betadex has been researched along with Neoplasms* in 84 studies
1 review(s) available for betadex and Neoplasms
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A New Approach for β-cyclodextrin Conjugated Drug Delivery System in Cancer Therapy.
Natural cyclodextrins (CDs) are macrocyclic starch molecules discovered a decade ago, in which α-, β-, and γ-CD were commonly used. They originally acted as pharmaceutical excipients to enhance the aqueous solubility and alter the physicochemical properties of drugs that fall under class II and IV categories according to the Biopharmaceutics Classification System (BPS). The industrial significance of CDs became apparent during the 1970s as scientists started to discover more of CD's potential in chemical modifications and the formation of inclusion complexes. CDs can help in masking and prolonging the half-life of drugs used in cancer. Multiple optimization techniques were discovered to prepare the derivatives of CDs and increase their complexation and drug delivery efficiency. In recent years, due to the advancement of nanotechnology in pharmaceutical sectors, there has been growing interest in CDs. This review mainly focuses on the formulation of cyclodextrin conjugated nanocarriers using graphenes, carbon nanotubes, nanosponges, hydrogels, dendrimers, and polymers to achieve drug-release characteristics specific to cells. These approaches benefit the discovery of novel anti-cancer treatments, solubilization of new drug compounds, and cell specific drug delivery properties. Due to these unique properties of CDs, they are essential in achieving and enhancing tumor-specific cancer treatment. Topics: beta-Cyclodextrins; Cyclodextrins; Drug Delivery Systems; Nanotubes, Carbon; Neoplasms; Pharmaceutical Preparations; Solubility | 2022 |
1 trial(s) available for betadex and Neoplasms
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Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors.
This study compares serum pharmacokinetics, urinary excretion patterns, and relative bioequivalencies of single doses of MitoExtra (ME; SuperGen, San Ramon, CA) and mitomycin C (MMC).. Thirty-five patients were entered into this open-label, single-institution, crossover study with 2 treatment arms. Each patient received alternating courses of ME and MMC as 15 mg/m(2) single intravenous doses via a short intravenous infusion. Patients were sequentially assigned to receive either ME or MMC as their first treatment course. The courses were given in 6-week intervals and could be repeated up to 4 times in patients with responding disease. Pharmacokinetic parameters were analyzed during the first two courses of therapy.. The noncompartmental pharmacokinetic analysis conducted on serum and urine data obtained from patients who received both ME and MMC indicates that the kinetic disposition of these two formulations is similar. This is evident when the mean (+/- standard deviation) values of the various pharmacokinetic parameters are compared. There were no significant differences in any of the kinetic parameters obtained between treatments in all patients examined. The statistical evaluation conducted on the 25 patients that completed both arms of the 2-way pharmacokinetic crossover demonstrates that ME is bioequivalent to MMC. Hematologic and nonhematologic toxicities were similar between the two treatments. There were three clinically significant infusion-related complications associated with MMC administration and none associated with ME.. The similar pharmacokinetics of MMC and ME suggest complete release of MMC from the hydroxypropyl-Beta-cyclodextrin carrier contained in the ME formulation. Further studies are needed to define the pharmacodynamics, toxicity, and efficacy of this drug-carrier complex. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; beta-Cyclodextrins; Cross-Over Studies; Cyclodextrins; Female; Humans; Male; Middle Aged; Mitomycin; Neoplasms; Therapeutic Equivalency | 2001 |
82 other study(ies) available for betadex and Neoplasms
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Ent-kaurenoic acid-enriched Mikania glomerata leaves-complexed β-cyclodextrin: Pharmaceutical development and in vivo antitumor activity in a sarcoma 180 mouse model.
The extract obtained from Mikania glomerata leaves rich in ent-kaurenoic acid (ERKA) shows cytotoxic activity in vitro, but its hydrophobic nature and thermosensitivity are issues to be solved prior to in vivo antitumor studies. The purpose of this study was to investigate the antitumor activity of inclusion complexes formed between ERKA and β-cyclodextrin (ERKA:β-CD) in rodents. ERKA:β-CD complexes obtained by malaxation (MX) and co-evaporation (CE) methods were firstly characterized regarding their physical properties, encapsulation efficiency, and cytotoxicity againts L929 cells. The antitumor activity study was then performed in mice with sarcoma 180 treated with saline, 5-fluouracil (5FU) and ERKA:β-CD at 30, 100 and 300 µg/kg. The weight, volume, percentage of inhibition growth, gross and pathological features and positivity for TUNEL, ki67, NFκB and NRF2 in the tumors were assessed. Serum lactate-dehydrogenase activity (LDH), white blood cells count (WBC) and both gross and pathological features of the liver, kidneys and spleen were also evaluated. The formation of the inclusion complexes was confirmed by thermal analysis and FTIR, and they were non-toxic for L929 cells. The MX provided a better complexation efficiency. ERKA:β-CD300 promoted significant tumor growth inhibition, and attenuated the tumor mitotic activity and necrosis content, comparable to 5-fluorouracil. ERKA:β-CD300 also increased TUNEL-detected cell death, reduced Ki67 and NF-kB immunoexpression, and partially inhibited the serum LDH activity. No side effect was observed in ERKA:β-CD300-treated animals. The ERKA:β-CD inclusion complexes at 300 µg/kg displays antitumour activity in mice with low systemic toxicity, likely due to inhibition on the NF-kB signaling pathway and LDH activity. Topics: Animals; beta-Cyclodextrins; Drug Development; Ki-67 Antigen; Mice; Mikania; Neoplasms; NF-kappa B; Sarcoma 180 | 2023 |
Interactions between β-cyclodextrin as a carrier for anti-cancer drug delivery: a molecular dynamics simulation study.
A series of molecular dynamics simulations were performed on 5-fluorouracil (5-Fu), Alendronate (Ald), and Temozolomide (TMZ) anticancer drugs in the presence and absence of β-cyclodextrin (βCD) as a carrier. Thermodynamic investigations showed that the van der Waals interaction energy was dominant in loading all drugs inside the βCD cavity. The sum of the interaction energies illustrated that the highest affinity was related to Ald (-136.5 kJ/mol), which in turn was due to the presence of bulky and charged atoms of phosphorus and oxygen, although TMZ (-115.92 kJ/mol) showed a very high affinity as well. At the same time, the hydrogen bond analysis also represented that Ald had the most hydrogen bond (1.97) with the highest half-life (3.13 ps) with βCD. Investigation of the root mean fluctuation (RMSF) indicated that all the drugs had a relatively rigid structure and maintain this rigidity during loading in the βCD cavity, and in the meantime, Ald was slightly more flexible than 5-Fu and TMZ. The area of the primary hydroxyl rim decreased in all drug-containing systems, which in turn was caused by the attractive interaction of drugs with oxygens in the primary hydroxyl rim. Especially for those drugs that were able to penetrate to the end of the primary hydroxyl rim of the βCD, that means TMZ and 5-Fu. Meanwhile, due to the lack of Ald penetration to the end of the primary hydroxyl rim, the area change in the Ald-containing system was less than in the two others.Communicated by Ramaswamy H. Sarma. Topics: Antineoplastic Agents; beta-Cyclodextrins; Drug Delivery Systems; Fluorouracil; Humans; Molecular Dynamics Simulation; Neoplasms | 2023 |
Antinociceptive Effect of a p-Cymene/β-Cyclodextrin Inclusion Complex in a Murine Cancer Pain Model: Characterization Aided through a Docking Study.
Pain is one of the most prevalent and difficult to manage symptoms in cancer patients, and conventional drugs present a range of adverse reactions. The development of β-cyclodextrins (β-CD) complexes has been used to avoid physicochemical and pharmacological limitations due to the lipophilicity of compounds such as p-Cymene (PC), a monoterpene with antinociceptive effects. Our aim was to obtain, characterize, and measure the effect of the complex of p-cymene and β-cyclodextrin (PC/β-CD) in a cancer pain model. Initially, molecular docking was performed to predict the viability of complex formation. Afterward, PC/β-CD was obtained by slurry complexation, characterized by HPLC and NMR. Finally, PC/β-CD was tested in a Sarcoma 180 (S180)-induced pain model. Molecular docking indicated that the occurrence of interaction between PC and β-CD is favorable. PC/β-CD showed complexation efficiency of 82.61%, and NMR demonstrated PC complexation in the β-CD cavity. In the S180 cancer pain model, PC/β-CD significantly reduced the mechanical hyperalgesia, spontaneous nociception, and nociception induced by non-noxious palpation at the doses tested ( Topics: Analgesics; Animals; beta-Cyclodextrins; Cancer Pain; Cyclodextrins; Humans; Mice; Molecular Docking Simulation; Neoplasms; Pain; Solubility | 2023 |
Enhancement in the therapeutic potential of lapatinib ditosylate against breast cancer by the use of β-cyclodextrin based ternary nanosponge system.
The present investigation was performed to demonstrate the therapeutic potential of lapatinib ditosylate (LD) loaded nanosponge for the treatment of breast cancer. The study reports the fabrication of nanosponge by reaction of β-cyclodextrin with a cross-linking agent, diphenyl carbonate, at several molar ratios using the ultrasound-assisted synthesis method. The drug was loaded into the rightest nanosponge by lyophilization with and without 0.25% w/w polyvinylpyrrolidone. The significantly reduced crystallinity of developed formulations was established by differential scanning calorimetry (DSC), and powder X-ray diffractometry (PXRD). Morphological changes of LD, and formulations were compared by scanning electron microscopic (SEM) technique. Fourier transform infrared (FT-IR), and nuclear magnetic resonance (NMR) spectroscopic analysis were performed to establish the interacting groups of the host and guest molecules. It revealed interaction of the quinazoline ring, furan ring, and chlorobenzene functionality of LD with the hydroxyl group of β-cyclodextrin based nanosponge. Similar predictions were also obtained during their in-silico analysis. Saturation solubility and in vitro drug release studies revealed a 4.03-fold, and 2.43-fold rise in aqueous solubility, and dissolution of LD in the optimized formula (F2). The MCF-7 cell line study, too, revealed the higher efficiency of nanosponge formulations. The in vivo pharmacokinetic studies of optimized formulation illustrated 2.76-times, and 3.34-times enhancements in C Topics: Animals; beta-Cyclodextrins; Calorimetry, Differential Scanning; Female; Lapatinib; Neoplasms; Rats; Rats, Sprague-Dawley; Solubility; Spectroscopy, Fourier Transform Infrared; X-Ray Diffraction | 2023 |
Adenosine/β-Cyclodextrin-Based Metal-Organic Frameworks as a Potential Material for Cancer Therapy.
Recently, researchers have employed metal-organic frameworks (MOFs) for loading pharmaceutically important substances. MOFs are a novel class of porous class of materials formed by the self-assembly of organic ligands and metal ions, creating a network structure. The current investigation effectively achieves the loading of adenosine (ADN) into a metal-organic framework based on cyclodextrin (CD) using a solvent diffusion method. The composite material, referred to as ADN:β-CD-K MOFs, is created by loading ADN into beta-cyclodextrin (β-CD) with the addition of K Topics: beta-Cyclodextrins; Cyclodextrins; gamma-Cyclodextrins; Humans; Metal-Organic Frameworks; Neoplasms; Spectroscopy, Fourier Transform Infrared | 2023 |
Stimulus-responsive drug/gene delivery system based on polyethylenimine cyclodextrin nanoparticles for potential cancer therapy.
Combination therapy through simultaneous delivery of anti-cancer drugs and genes with nano-assembled structure has been proved to be a simple and effective approach for treating breast cancer. In this study, redox-sensitive folate-appended-polyethylenimine-β-cyclodextrin (roFPC) host-guest supramolecular nanoparticles (HGSNPs) were developed as a targeted co-delivery system of doxorubicin (Dox) and Human telomerase reverse transcriptase-small interfering RNA) hTERT siRNA) for potential cancer therapy. The nanotherapeutic system was prepared by loading adamantane-conjugated doxorubicin (Ad-Dox) into roFPC through the supramolecular assembly, followed by electrostatically-driven self-assembly between hTERT siRNA and roFPC/Ad-Dox. The roFPC' host-guest structures allow pH-dependent intracellular drug release in a sustained manner, as well as simultaneous and effective gene transfection. This co-delivery vector displayed combined anti-tumor properties of the Dox-enhanced gene transfection, good water-solubility, and biocompatibility, possesses considerably enhanced hemocompatibility, and especially targets folate receptor-positive cells only at low N/P levels to prompt effective cell apoptosis for cancer treatment. Topics: Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Cyclodextrins; Doxorubicin; Drug Delivery Systems; Drug Liberation; Folic Acid; Gene Transfer Techniques; Humans; MCF-7 Cells; Nanoparticles; Neoplasms; Polyethyleneimine; RNA, Small Interfering | 2022 |
A Hybrid Supramolecular Polymeric Nanomedicine for Cascade-Amplified Synergetic Cancer Therapy.
Supramolecular nanomedicines have shown great merits in cancer therapy, but their clinical translation is hampered by monotonous therapeutic modality and unsatisfactory antitumor performance. Herein, a hybrid supramolecular polymeric nanomedicine (SNPs) is developed based on β-cyclodextrin/camptothecin (CPT) host-guest molecular recognition and iron-carboxylate coordination. Iron ions stabilizing SNPs catalyze the conversion of intracellular hydrogen peroxide into highly toxic hydroxyl radical through a Fenton reaction, which further cleaves the thioketal linker of the supramolecular monomer to release potent CPT, thus amplifying the therapeutic efficacy by combining chemodynamic therapy and chemotherapy. The combination therapy stimulates antitumor immunity and promotes intratumoral infiltration of cytotoxic T lymphocytes by triggering immunogenic cell death. In synergy with PD-L1 checkpoint blockade, SNPs enables enhanced immune therapy and a long-term tumor remission. Topics: beta-Cyclodextrins; Camptothecin; Cell Line, Tumor; Humans; Iron; Nanomedicine; Nanoparticles; Neoplasms; Polymers | 2022 |
PtBi-β-CD-Ce6 Nanozyme for Combined Trimodal Imaging-Guided Photodynamic Therapy and NIR-II Responsive Photothermal Therapy.
Topics: beta-Cyclodextrins; Cell Line, Tumor; Humans; Hydrogen Peroxide; Hypoxia; Nanoparticles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Photothermal Therapy; Tumor Microenvironment | 2022 |
Poly(β-cyclodextrin)/platinum prodrug supramolecular nano system for enhanced cancer therapy: Synthesis and in vivo study.
Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Cisplatin; Mice; Neoplasms; Platinum; Prodrugs; Propylene Glycols | 2022 |
γ-Terpinene complexed with β-cyclodextrin attenuates spinal neuroactivity in animals with cancer pain by Ca2+ channel block.
Considering that γ-terpinene (γ-TPN) is a monoterpene found in Cannabis oil, with high lipophilicity and limited pharmacokinetics, our objective was to evaluate whether its complexation in β-cyclodextrin (γ-TPN/β-CD) could improve its physicochemical properties and action on cancer pain, as well as verify the mechanisms of action involved.. The γ-TPN/β-CD was prepared and submitted to physicochemical characterization. Animals with sarcoma 180 were treated (vehicle, γ-TPN 50 mg/kg, γ-TPN/β-CD 5 mg/kg or morphine) and assessed for hyperalgesia, TNF-α and IL-1β levels, iNOS and c-Fos activity. The effects of γ-TPN on calcium channels were studied by patch-clamp and molecular docking.. β-CD improved the physicochemical properties and prolonged the anti-hyperalgesic effect of γ-TPN. This compound also reduced the levels of IL-1β, TNF-α and iNOS in the tumour, and c-Fos protein in the spinal cord. In addition, it reduced Ca2+ current, presenting favourable chemical interactions with different voltage-dependent calcium channels.. These results indicate that the complexation of γ-TPN into β-CD increases its stability and time effect, reducing spinal neuroactivity and inflammation by blocking calcium channels. Topics: Animals; beta-Cyclodextrins; Calcium; Calcium Channels; Cancer Pain; Hyperalgesia; Molecular Docking Simulation; Neoplasms; Proto-Oncogene Proteins c-fos; Tumor Necrosis Factor-alpha | 2022 |
In vivo investigation of Gallium-68 and Bismuth-205/206 labeled beta cyclodextrin for targeted alpha therapy of prostaglandin E2 receptor-expressing tumors in mice.
Prostaglandin E2 (PGE2) molecule and its receptors play an important role in the development of malignancies and metastases therefore PGE2 may play a crucial role in the diagnosis and a new therapeutic target in the field of radionuclide therapy of PGE2-positive tumors. PGE2 form complexes with RAMEB (randomly-methylated-beta-cyclodextrin) with high affinity therefore the aim of this present study was to synthesize a PGE2-specific DOTAGA-RAMEB, which can be labeled with diagnostic and therapeutic isotopes also and binds to PGE2-positive tumors. DOTAGA-RAMEB was labeled with Topics: Animals; beta-Cyclodextrins; Bismuth; Cell Line, Tumor; Dinoprostone; Gallium Radioisotopes; Mice; Mice, SCID; Neoplasms; Positron-Emission Tomography; Radioisotopes; Receptors, Prostaglandin; Tissue Distribution | 2022 |
Supramolecular Dual Polypeptides Induced Tubulin Aggregation for Synergistic Cancer Theranostics.
The advent of macrocycle-based supramolecular chemistry can offer powerful strategies for regulating vital bioactivities in living systems and bring about emerging technology in biomedical science. Herein, we construct a supra-biomacromolecular nanosystem involving microtubules, cell-permeable porphyrins, and antimitotic peptide-decorated permethyl-β-cyclodextrins for promoting cell apoptosis in a cooperative manner. Through specific polypeptide-tubulin recognition, cyclodextrin moieties are capable of anchoring to the tubulin surface and providing abundant hydrophobic microenvironments to accommodate the photosensitive porphyrins. Consequently, spherical tubulin aggregates are formed, and reactive oxygen species can be efficiently generated via the host-guest complexation. The combined usage of complexation-promoted photodynamic efficacy and tubulin aggregation gives more serious cell apoptosis under light irradiation in vitro and in vivo. To be envisioned, this supramolecularly enhanced photodynamic performance together with controlled aggregation of natural biomacromolecules may be developed as an innovative approach to improve the therapeutic potency against many diseases. Topics: Antimitotic Agents; beta-Cyclodextrins; Cyclodextrins; Humans; Neoplasms; Peptides; Porphyrins; Precision Medicine; Reactive Oxygen Species; Tubulin; Tumor Microenvironment | 2022 |
Mass Spectrometric Evaluation of β-Cyclodextrins as Potential Hosts for Titanocene Dichloride.
Bent metallocene dichlorides (Cp Topics: beta-Cyclodextrins; Humans; Mass Spectrometry; Molecular Structure; Neoplasms; Organometallic Compounds | 2021 |
Novel pH-Triggered Doxorubicin-Releasing Nanoparticles Self-Assembled by Functionalized β-Cyclodextrin and Amphiphilic Phthalocyanine for Anticancer Therapy.
Cyclodextrins (CDs), as pharmaceutical excipients with excellent biocompatibility, non-immunogenicity, and low toxicity in vivo, are widely used to carry drugs by forming inclusion complexes for improving the solubility and stability of drugs. However, the limited space of CDs' lipophilic central cavity affects the loading of many drugs, especially with larger molecules. In this study, β-CDs were modified by acetonization to improve the affinity for the chemotherapy drug doxorubicin (DOX), and doxorubicin-adsorbing acetalated β-CDs (Ac-CD:DOX) self-assembled to nanoparticles, followed by coating with the amphiphilic zinc phthalocyanine photosensitizer ZnPc-(PEG) Topics: Animals; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Doxorubicin; Drug Carriers; Drug Liberation; Drug Synergism; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Indoles; Isoindoles; Light; Male; Membrane Potential, Mitochondrial; Mice; Mitochondria; Nanoparticles; Neoplasms; Organometallic Compounds; Photosensitizing Agents; Reactive Oxygen Species; Zinc Compounds | 2021 |
Exploring Charged Polymeric Cyclodextrins for Biomedical Applications.
Over the years, cyclodextrin uses have been widely reviewed and their proprieties provide a very attractive approach in different biomedical applications. Cyclodextrins, due to their characteristics, are used to transport drugs and have also been studied as molecular chaperones with potential application in protein misfolding diseases. In this study, we designed cyclodextrin polymers containing different contents of β- or γ-cyclodextrin, and a different number of guanidinium positive charges. This allowed exploration of the influence of the charge in delivering a drug and the effect in the protein anti-aggregant ability. The polymers inhibit Amiloid β peptide aggregation; such an ability is modulated by both the type of CyD cavity and the number of charges. We also explored the effect of the new polymers as drug carriers. We tested the Doxorubicin toxicity in different cell lines, A2780, A549, MDA-MB-231 in the presence of the polymers. Data show that the polymers based on γ-cyclodextrin modified the cytotoxicity of doxorubicin in the A2780 cell line. Topics: A549 Cells; beta-Cyclodextrins; Cellulose; Cyclodextrins; Doxorubicin; Drug Carriers; gamma-Cyclodextrins; Humans; Neoplasms | 2021 |
Supramolecular Polymerization-Induced Nanoassemblies for Self-Augmented Cascade Chemotherapy and Chemodynamic Therapy of Tumor.
Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Coordination Complexes; Drug Carriers; Drug Liberation; Female; Ferrous Compounds; Hydrogen Peroxide; Hydroxyl Radical; Metallocenes; Mice, Inbred BALB C; Nanomedicine; Nanoparticles; Neoplasms; Platinum; Polymerization; Polymers; Prodrugs | 2021 |
A Novel Folic Acid Receptor-Targeted Drug Delivery System Based on Curcumin-Loaded β-Cyclodextrin Nanoparticles for Cancer Treatment.
A novel folate receptor-targeted β-cyclodextrin (β-CD) drug delivery vehicle was constructed to improve the bioavailability, biosafety, and drug loading capacity of curcumin. Controlled release and targeted delivery was achieved by modifying the nanoparticles with folic acid (FA).. Folate-conjugated β-CD-polycaprolactone block copolymers were synthesized and characterized. Curcumin-loaded nanoparticles (FA-Cur-NPs) were structured by self-assembly. The physicochemical properties, stability, release behavior and tumor-targeting ability of the fabricated nanoparticles were studied.. The average particle size and drug loading of FA-Cur-NPs was 151.8 nm and 20.27%, respectively. Moreover, the FA-Cur-NPs exhibited good stability in vitro for 72 h. The drug release profiles showed that curcumin from FA-Cur-NPs was released significantly faster in a pH 6.4 phosphate buffered solution (PBS) than in pH 7.4, indicating that curcumin can be enriched around the tumor site compared with normal cells. Additionally, the internalization of FA-Cur-NPs was aided by FA receptor-mediated endocytosis, and its cytotoxicity was proportional to the cellular uptake efficiency. Furthermore, in vivo studies confirmed that FA-Cur-NPs exhibited marked accumulation in the tumor site and excellent antitumor activity.. These findings suggest that FA-Cur-NPs are a promising approach for improving cancer therapy through active targeting and controllable release. Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Curcumin; Drug Carriers; Drug Delivery Systems; Drug Liberation; Female; Folate Receptors, GPI-Anchored; Folic Acid; HeLa Cells; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms; Particle Size; Polyesters; Tissue Distribution; Xenograft Model Antitumor Assays | 2021 |
Acid-Sensitive Supramolecular Nanoassemblies with Multivalent Interaction: Effective Tumor Retention and Deep Intratumor Infiltration.
It remains a conundrum to reconcile the contradiction between effective tumor retention and deep intratumor infiltration for nanotherapeutics due to the sophisticated drug delivery journey. Herein, we reported an acid-sensitive supramolecular nanoassemblies (DCD SNs) based on the multivalent host-gest inclusions of two polymer conjugates for conquering diverse physiological blockages and amplifying therapeutic efficacy. The multiple inclusions of repetitive units on the hydrophilic polymer backbone reinforced the binding affinity and induced robust self-assembly, ameliorating instability of the self-assemblies and facilitating to prolong the drug retention time. By virtue of the acid-sensitive Schiff base linkages, the supramolecular nanoassembly could respond to the unique tumor microenvironment (TME), dissociate, and transform into smaller particles (∼30 nm), thereby efficiently traversing the complicated extracellular matrix and irregular blood vessels to achieve deep intratumor infiltration. The acid-sensitive DCD SNs can absorb a large number of protons in the acidic lysosomal environment, causing the proton sponge effect, which was conducive to their escape from endolysosomes and accelerated lysosomal disruption, so that the active chemotherapeutic doxorubicin (DOX) could enter the nucleus well and exert severe DNA damage to induce apoptosis. This versatile supramolecular nanoplatform is anticipated to be a promising candidate to overcome the limitations of insufficient stability within the circulation and weak intratumor penetration. Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Dextrans; DNA Damage; Doxorubicin; Drug Carriers; Drug Liberation; Female; Lysosomes; Macromolecular Substances; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Rats, Sprague-Dawley | 2021 |
Deoxycholic acid induces proinflammatory cytokine production by model oesophageal cells via lipid rafts.
The bile acid component of gastric refluxate has been implicated in inflammation of the oesophagus including conditions such as gastro-oesophageal reflux disease (GORD) and Barrett's Oesophagus (BO). Here we demonstrate that the hydrophobic bile acid, deoxycholic acid (DCA), stimulated the production of IL-6 and IL-8 mRNA and protein in Het-1A, a model of normal oesophageal cells. DCA-induced production of IL-6 and IL-8 was attenuated by pharmacologic inhibition of the Protein Kinase C (PKC), MAP kinase, tyrosine kinase pathways, by the cholesterol sequestering agent, methyl-beta-cyclodextrin (MCD) and by the hydrophilic bile acid, ursodeoxycholic acid (UDCA). The cholesterol-interacting agent, nystatin, which binds cholesterol without removing it from the membrane, synergized with DCA to induce IL-6 and IL-8. This was inhibited by the tyrosine kinase inhibitor genistein. DCA stimulated the phosphorylation of lipid raft component Src tyrosine kinase (Src). while knockdown of caveolin-1 expression using siRNA resulted in a decreased level of IL-8 production in response to DCA. Taken together, these results demonstrate that DCA stimulates IL-6 and IL-8 production in oesophageal cells via lipid raft-associated signaling. Inhibition of this process using cyclodextrins represents a novel therapeutic approach to the treatment of inflammatory diseases of the oesophagus including GORD and BO. Topics: Barrett Esophagus; beta-Cyclodextrins; Bile Acids and Salts; Caveolin 1; Cell Line, Tumor; Cholesterol; Cytokines; Deoxycholic Acid; Esophagus; Gastroesophageal Reflux; Gene Expression; Humans; Inflammation; Interleukin-6; Interleukin-8; Lipids; Membrane Microdomains; Neoplasms; NF-kappa B; Phosphorylation; Signal Transduction; src-Family Kinases | 2021 |
Facile construction of shape-regulated β-cyclodextrin-based supramolecular self-assemblies for drug delivery.
Although supramolecular prodrug self-assemblies have been proven as efficient nanocarriers for cancer therapy, tedious synthesis procedures have made their practical applications more difficult. In this paper, β-cyclodextrin-based supramolecular self-assemblies (SSAs) were directly constructed by utilizing β-cyclodextrin trimer (β-CD Topics: Apoptosis; beta-Cyclodextrins; Cell Proliferation; Curcumin; Delayed-Action Preparations; Doxorubicin; Drug Delivery Systems; Drug Liberation; HeLa Cells; Humans; MCF-7 Cells; Micelles; Neoplasms | 2020 |
Fluorescent Metallacycle-Cored Amphiphilic Nanoparticles Formed by β-Cyclodextrin-Based Host-Guest Interactions towards Cancer Theranostics.
Theranostic agents, taking the advantages of both imaging and therapeutic functions, are anticipated to be key components in the development of personalized medicine in which the therapeutic response can be real-time monitored. Herein, three metallacycles with pendent adamantane groups are prepared by coordination-driven self-assembly of Pt Topics: beta-Cyclodextrins; Humans; Nanoparticles; Neoplasms; Precision Medicine; Rhodamines | 2020 |
Multifunctional nanoparticles of paclitaxel and cyclodextrin-polypeptide conjugates with
In this study, the cyclodextrin polypeptide (R8-CMβCD) was successfully synthesized by the conjugation of a cell-penetrating peptide (R8) with carboxymethyl-β-cyclodextrin (CMβCD) via the carbon diamine reaction. Then, paclitaxel-loaded nanoparticles (PTX@R8-CMβCD NPs) was prepared. Results of transmission electron microscopy (TEM) showed that PTX@R8-CMβCD NPs were spherical with smooth surfaces and an average diameter about 144 nm. The amount of PTX released from NPs was less than 20% at pH7.4, but it increased significantly to 80% in the weakly acidic cytoplasm of tumors (pH5.0). Furthermore, PTX@R8-CMβCD NPs promoted the cellular uptake of PTX. Further studies on the mechanism showed that cellular uptake of PTX@R8-CMβCD NPs could rely on multiple pathways. In addition, the NPs had the ability to inhibit P-gp efflux pumps. Cytotoxicity tests showed that the NPs had no side effects. Taken together, PTX@R8-CMβCD NPs is an effective anticancer drug delivery system, and the material (R8-CMβCD) may be a promising anti-cancer drug carrier. Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line; Cell Line, Tumor; Cell-Penetrating Peptides; Cyclodextrins; Drug Delivery Systems; HEK293 Cells; Humans; MCF-7 Cells; Mice; Multifunctional Nanoparticles; Neoplasms; Paclitaxel; Peptides | 2020 |
Cyclodextrin based unimolecular micelles with targeting and biocleavable abilities as chemotherapeutic carrier to overcome drug resistance.
An amphiphilic star-shaped copolymer β-CD-g-PCL-SS-PEG-FA, consisting of a β-cyclodextrin (β-CD) core as well as grafted with bioreducible disulfide linkage in PCL-SS-PEG multiarms and targeting folic acid (FA) as end moiety, is designed with unimolecular micelles formation ability for targeted transport of chemotherapeutics to drug resistant tumor cells. Firstly, β-CD was utilized as core to growth PCL arms by ring-opening polymerization (ROP) of ε-CL, before disulfide terminal group transformation to render β-CD-g-PCL-SS-COOH. Secondly, α-hydroxy-ω-amine protected PEG (HO-PEG-NHBoc) was connected to β-CD-g-PCL-SS-COOH to obtain amphiphilic β-CD-g-PCL-SS-PEG, where PCL and PEG were connected via bioreducible disulfide bond. After deprotection of -Boc group, FA was introduced onto the distal end of block arms to obtain the desired β-CD-g-PCL-SS-PEG-FA copolymer. Because of highly branched core-shell amphiphilic structures, β-CD-g-PCL-SS-PEG-FA could act as unimolecular micelles. Interestingly, this unimolecular micelle could release the encapsulated drug in a glutathione (GSH) dependent manner due to disulfide linkage. More importantly, this unimolecular micelle could load doxorubicin (DOX) to promote its cellular uptake in multidrug resistance (MDR) protein overexpression tumor cells, by taking the advantage of FA targeting group and intracellular high GSH level in cancer cells. Together with satisfactory biocompatibility, this novel star-like β-CD-g-PCL-SS-PEG-FA unimolecular micelle could potentially be utilized as targeting nanocarriers in drug resistant cancer therapy. Topics: beta-Cyclodextrins; Delayed-Action Preparations; Doxorubicin; Drug Carriers; Drug Resistance, Neoplasm; HeLa Cells; Hep G2 Cells; Humans; Micelles; Neoplasms | 2019 |
A tungsten nitride-based degradable nanoplatform for dual-modal image-guided combinatorial chemo-photothermal therapy of tumors.
An innovative tungsten-based multifunctional nanoplatform composed of polyethylene glycol (PEG)-modified tungsten nitride nanoparticles (WN NPs) is constructed for tumor treatment. The PEG-WN NPs not only possess strong near-infrared (NIR) absorbance, high photothermal conversion efficiency, and excellent photothermal stability, but also effectively inhibit tumor cells upon 808 nm laser irradiation. After coating with thiolated (2-hydroxypropyl)-β-cyclodextrin (MUA-CD) on the surface, such a nanoplatform can also be used for drug delivery (such as DOX) and presents a synergistic tumor inhibition effect both in vitro and in vivo. Furthermore, the PEG-WN NPs present good contrasting capability for X-ray computed tomography (CT) and photoacoustic (PA) imaging. With PA/CT imaging, the tumor can be accurately positioned for precise treatment. It is worth mentioning that PEG-WN NPs are biodegradable and could be effectively excreted from the body with no appreciable toxicity in vivo. It is expected that this biocompatible multifunctional nanoplatform can serve as a potential candidate for tumor treatment in future clinical applications. Topics: Animals; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Female; Hyperthermia, Induced; Lasers; Metal Nanoparticles; Mice; Mice, Inbred BALB C; Neoplasms; Particle Size; Photoacoustic Techniques; Phototherapy; Polyethylene Glycols; Theranostic Nanomedicine; Tomography, X-Ray Computed; Tungsten | 2019 |
A tumor-targeting Ru/polysaccharide/protein supramolecular assembly with high photodynamic therapy ability.
Supramolecular assembly with tumor-targeting properties or photodynamic therapy (PDT) ability has recently become a focus of interest in biomaterial field because of its high therapeutic efficacy against tumor cells. Herein, we reported a new type of targeted supramolecular nanoparticles for photodynamic therapy of tumor cells constructed using adamantane-functionalized transferrin protein (Ad-TRF) and a β-cyclodextrin-functionalized ruthenium complex (Ru-HOP-CD), wherein Ad-TRFs acted as the targeted sites for tumor cells, the coordinated Ru(ii) centers acted as the PDT active sites, and the biocompatible polysaccharide β-cyclodextrins acted as the non-covalent linkers. Significantly, the resultant Ru/polysaccharide/protein exhibited not only specific targeting properties towards tumor cells but also high PDT ability under the irradiation of visible light. Furthermore, the assembly showed selective killing towards tumor cells along with negligible toxicity towards normal cells. Topics: A549 Cells; Adamantane; beta-Cyclodextrins; Cell Line; Coordination Complexes; Drug Delivery Systems; Humans; Models, Molecular; Neoplasms; Photochemotherapy; Photosensitizing Agents; Ruthenium; Transferrin | 2019 |
Development of gold-core silica shell nanospheres coated with poly-2-ethyl-oxazoline and β-cyclodextrin aimed for cancer therapy.
Cancer is one of the major world public health problems and the currently available treatments are nonspecific and ineffective. This reality highlights the importance of developing novel therapeutic approaches. In this field, multifunctional nanomedicines have the potential to revolutionize the currently available treatments. These unique nanodevices can simultaneously act as therapeutic and imaging agents allowing the real-time monitoring of the nanoparticles biodistribution and the treatment outcome. Among the different nanoparticles, the gold-core silica shell (AuMSS) nanoparticles advantageous physicochemical and biological properties make them promising nanoplatforms for cancer therapy. Nevertheless, their successful application as an effective cancer nanomedicine is limited by the unfavorable pharmacokinetics and uncontrolled release of the therapeutic payloads. Herein, a new polymeric coating for AuMSS nanospheres was developed by combining different ratios (25/75, 50/50 and 75/25) of two materials, Poly-2-ethyl-2-oxazoline (PEOZ) and β-cyclodextrin (β-CD). The surface functionalization of AuMSS nanospheres led to a size increase and to the neutralization of the surface charge. On the other side, the nanoparticles biological performance was improved. The coated AuMSS nanospheres showed an increased cytocompatibility and internalization rate by the HeLa cancer cells. Overall, the obtained data confirm the successful modification of the AuMSS nanospheres with PEOZ and β-CD as well as their promising properties for being applied in cancer therapy. Topics: Animals; beta-Cyclodextrins; Cell Movement; Fibroblasts; Gold; HeLa Cells; Hemolysis; Humans; Mice; Nanoparticles; Nanospheres; Neoplasms; Polyamines; Silicon Dioxide | 2019 |
Preparation, optimization of the inclusion complex of glaucocalyxin A with sulfobutylether-β-cyclodextrin and antitumor study.
Glaucocalyxin A (GLA), is a diterpenoid extracted from Hara and has been studied for decades for its diverse bioactivities. However, GLA presents poor solubility in water and low bioavailability through oral administration which has hindered its application in the clinic. So in this study, we prepared the inclusion complex of GLA in SBE-β-CD by ultrasound method and evaluated its antitumor effect and cytotoxic effect on cancer cells. The production of GLA-SBE-β-CD inclusion complex was optimized using Box-Behnken design. The inhibitory effects of GLA and GLA-SBE-β-CD were investigated on the Hela, A549, HepG2, and SiHa cells in vitro by MTT staining assay. Pharmacokinetic studies were conducted on Sprague-Dawley mice via caudal injection to study the distribution, metabolism, and elimination of GLA-SBE-β-CD in vivo. Tumor-bearing nude mice were taken as the model and adopted to evaluate the inhibitory rate of GLA and GLA-SBE-β-CD on the transplanted tumor. A series of physical characterization results confirmed the fact that GLA-SBE-β-CD inclusion complex was successfully prepared. A production of 87.28% was achieved based on the Box-Behnken design. In the cancer cell inhibition studies, GLA and GLA-SBE-β-CD exhibited apparent concentration-dependent inhibitory actions on four kinds of tumor cells and better inhibition was achieved in GLA-SBE-β-CD group. The pharmacokinetic results showed that the duration of GLA in blood was prolonged and enhanced bioavailability was achieved. GLA and GLA-SBE-β-CD both showed an effective inhibition on the transplanted tumor growth, while the anti-tumor effect of GLA-SBE-β-CD (inhibitory rate of 45.80%) was significantly stronger than that of GLA (30.76%) based on the change of tumor weight and tumor volume. Topics: A549 Cells; Administration, Oral; Animals; Antineoplastic Agents; beta-Cyclodextrins; Biological Availability; Chemistry, Pharmaceutical; Diterpenes, Kaurane; Dose-Response Relationship, Drug; Drug Carriers; Drug Compounding; Female; HeLa Cells; Hep G2 Cells; Humans; Male; Mice; Mice, Nude; Neoplasms; Rats; Rats, Sprague-Dawley; Solubility | 2019 |
Co-responsive smart cyclodextrin-gated mesoporous silica nanoparticles with ligand-receptor engagement for anti-cancer treatment.
Combination of both internal- and external-stimuli responsive strategies in nanoplatforms can maximize therapeutic outcomes by overcoming drug efflux-mediated resistance and prolonging sustained release of therapeutic payloads in controlled and sequential manner. Here, we show a light/redox dual-stimuli responsive β-cyclodextrin (β-CD)-gated mesoporous silica nanoparticles (MSN) that can effectively load and seal the chemotherapeutics, doxorubicin (DOX), inside MSN with a dual-capped system. The primary gatekeeper was achieved by capping β-CD via a disulfide linkage. An azobenzene/galactose-grafted polymer (GAP) was introduced to functionalize the MSN surface through host-guest interaction. GAP not only served as a secondary non-covalent polymer-gatekeeper to further prevent molecules from leaking out, but also presented targeting ligand for engagement of the asialoglycoprotein receptor (ASGPR) on hepatocellular carcinoma (HepG2) cells. The controlled and stimuli release of DOX could be realized via dissociation of azobenzene moieties from β-CD cage upon UV-irradiation, followed by liberation with the endogenous glutathione. The in vitro studies verified the redox-sensitive DOX release behavior, and the UV irradiation could accelerate this process to trigger DOX burst from MSN-ss-CD/GAP. Notably, the DOX@MSN-ss-CD/GAP could more efficiently deliver DOX into HepG2 cells and demonstrate enhanced cytotoxicity as compared with HeLa and COS7 cells. The smart MSN-ss-CD/GAP delivery system holds the potential for universal therapeutic uses in both biomedical research and clinical settings. Topics: Animals; Antineoplastic Agents; Asialoglycoprotein Receptor; beta-Cyclodextrins; Chlorocebus aethiops; COS Cells; Doxorubicin; Drug Carriers; HeLa Cells; Hep G2 Cells; Humans; Nanoparticles; Neoplasm Proteins; Neoplasms; Porosity; Silicon Dioxide; Ultraviolet Rays | 2019 |
Polyrotaxane-based supramolecular theranostics.
The development of smart theranostic systems with favourable biocompatibility, high loading efficiency, excellent circulation stability, potent anti-tumour activity, and multimodal diagnostic functionalities is of importance for future clinical application. The premature burst release and poor degradation kinetics indicative of polymer-based nanomedicines remain the major obstacles for clinical translation. Herein we prepare theranostic shell-crosslinked nanoparticles (SCNPs) using a β-cyclodextrin-based polyrotaxane (PDI-PCL-b-PEG-RGD⊃β-CD-NH Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Cyclodextrins; Doxorubicin; Drug Delivery Systems; Female; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms; Poloxamer; Positron Emission Tomography Computed Tomography; Rotaxanes; Theranostic Nanomedicine | 2018 |
Supramolecular glyco-poly-cyclodextrin functionalized thin-layer manganese dioxide for targeted stimulus-responsive bioimaging.
We have developed a supramoleuclar imaging probe based on thin-layer manganese dioxide functionalized with a fluorescent, multivalent glyco-poly-cycolodextrin for the targeted, stimulus-responsive bioimaging of cancer cells. Topics: Acrylamides; Adamantane; Asialoglycoprotein Receptor; beta-Cyclodextrins; Cell Line, Tumor; Drug Stability; Fluorescent Dyes; Humans; Lectins, C-Type; Ligands; Macromolecular Substances; Manganese Compounds; Mannose Receptor; Mannose-Binding Lectins; Naphthalimides; Neoplasms; Oxides; Receptors, Cell Surface | 2018 |
Water-soluble fluorescent unimolecular micelles: ultra-small size, tunable fluorescence emission from the visible to NIR region and enhanced biocompatibility for in vitro and in vivo bioimaging.
Fluorescent unimolecular micelles (FUMs) with multicolor emission acting as fluorescent nanoagents for optical fluorescence imaging have, for the first time, been reported. The FUMs show good water-solubility, ultra-small size, and enhanced biocompatibility, which endow the FUMs with versatile applications including organelle labeling, multicolor markers and high tumor accumulation, revealing that our design can serve as a rational strategy for the development of UM-based fluorescent nanoagents for bioprocess monitoring. Topics: Animals; beta-Cyclodextrins; Biocompatible Materials; Carbocyanines; Cell Line, Tumor; Cytoskeleton; Female; Fluoresceins; Fluorescence; Fluorescent Dyes; Humans; Lysosomes; Methacrylates; Mice, Inbred BALB C; Micelles; Mitochondria; Neoplasms; Particle Size; Polyethylene Glycols; Rhodamines; Solubility | 2018 |
Supramolecular Polymer-Based Nanomedicine: High Therapeutic Performance and Negligible Long-Term Immunotoxicity.
Nanomedicines have achieved several breakthroughs in cancer treatment over the past decades; however, their potential immunotoxicities are ignored, which results in serious adverse effects and greatly reduces the potential in clinical translation. Herein, we innovatively develop a theranostic supramolecular polymer using β-cyclodextrin as the host and camptothecin (CPT) as the guest linked by a glutathione-cleavable disulfide bond. The supramolecular polymerization remarkably increases the solubility of CPT by a factor of 232 and effectively inhibits its lactone ring opening in physiological environment, which is favorable for intravenous formulation and maintenance of the therapeutic efficacy. Supramolecular nanoparticles can be prepared through orthogonal self-assembly driven by π-π stacking interaction, host-guest complexation, and hydrogen bonds. The sophisticated nanomedicine constructed from the obtained supramolecular polymer can be specifically delivered to tumor sites and rapidly excreted from body after drug release, thus effectively avoiding systemic toxicity, especially long-term immunotoxicity. In vivo investigations demonstrate this supramolecular nanomedicine possesses superior antitumor performance and antimetastasis capability. This pioneering example integrating the advantages of the dynamic nature of supramolecular chemistry and nanotechnology provides a promising platform for cancer theranostics. Topics: Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Breast Neoplasms; Camptothecin; Female; Glutathione; HeLa Cells; Humans; Nanomedicine; Neoplasms; Positron-Emission Tomography; Solubility | 2018 |
One-pot fabrication of pH/reduction dual-stimuli responsive chitosan-based supramolecular nanogels for leakage-free tumor-specific DOX delivery with enhanced anti-cancer efficacy.
Topics: beta-Cyclodextrins; Chitosan; Doxorubicin; Drug Delivery Systems; Gels; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Nanostructures; Neoplasms | 2018 |
A liposome preparation based on β-CD-LPC molecule and its application as drug-delivery system.
The β-CD-LPC molecule was synthesized based on the conjugation of LPC and β-CD molecules and it could self-assemble into liposome which was used to encapsulate the Dox to form nanomedicine for the cancer therapy.. The anticancer and antitumor effect of β-CD-LPC-Dox nanomedicine was studied with the vitro and vivo experimental methods.. The result showed that β-CD-LPC liposome had high Dox drug-loading rate and a good sustained-release effect. Cell experiment showed that the β-CD-LPC-Dox nanomedicine could effectively induce cancer cell apoptosis and in vivo experiments showed that β-CD-LPC-Dox liposome could effectively inhibit tumor growth and had an effective anticancer activity with lower biotoxicity.. The β-CD-LPC-Dox nanomedicine could be applied as a candidate drug to therapy the cancer. Topics: Animals; Apoptosis; beta-Cyclodextrins; Cell Proliferation; Doxorubicin; Drug Delivery Systems; Hep G2 Cells; Humans; Liposomes; MCF-7 Cells; Mice; Neoplasms; Xenograft Model Antitumor Assays | 2018 |
Construction of a High-Efficiency Drug and Gene Co-Delivery System for Cancer Therapy from a pH-Sensitive Supramolecular Inclusion between Oligoethylenimine- graft-β-cyclodextrin and Hyperbranched Polyglycerol Derivative.
Introducing genes into drug-delivery system for a combined therapy has become a promising strategy for cancer treatment. However, improving the in vivo therapy effect resulted from the high delivery efficiency, low toxicity, and good stability in the blood remains a challenge. For this purpose, the supramolecular inclusion was considered to construct a high-efficiency drug and gene co-delivery system in this work. The oligoethylenimine-conjugated β-cyclodextrin (β-CD-PEI600) and benzimidazole-modified four-arm-polycaprolactone-initiated hyperbranched polyglycerol (PCL-HPG-BM) were synthesized as the host and guest molecules, respectively, and then the co-delivery carrier of PCL-HPG-PEI600 was formed from the pH-mediated inclusion interaction between β-CD and BM. PCL-HPG-PEI600 showed the improved drug (doxorubicin, DOX) and gene (MMP-9 shRNA plasmid, pMMP-9) delivery ability in vivo, and their cellular uptake and intracellular delivery were investigated. Particularly, PCL-HPG-PEI600 showed excellent pMMP-9 delivery ability with significantly higher transfection efficiency than PEI25k due to its excellent serum resistance. For the combined therapy to breast cancer MCF-7 tumor, the co-delivery system of PCL-HPG-PEI600/DOX/pMMP-9 resulted in a much better inhibition effect on MCF-7 cell proliferation and migration in vitro as well as the suppression effect on MCF-7 tumors in vivo compared to those of single DOX or pMMP-9 formulation used. Moreover, PCL-HPG-PEI600 displayed nontoxicity and excellent blood compatibility, suggesting a promising drug and gene co-delivery carrier in combined therapy to tumors. Topics: Animals; beta-Cyclodextrins; Biocompatible Materials; Cell Movement; Doxorubicin; Drug Delivery Systems; Drug Liberation; Endocytosis; Endosomes; Female; Gene Transfer Techniques; Glycerol; Humans; Hydrogen-Ion Concentration; Matrix Metalloproteinase 9; MCF-7 Cells; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasms; Polyesters; Polyethyleneimine; Polymers; Transfection | 2018 |
Tumor Targeting and Lipid Rafts Disrupting Hyaluronic Acid-Cyclodextrin-Based Nanoassembled Structure for Cancer Therapy.
CD44 receptor targeting and lipid rafts destroying nanoassembly (NA) was developed for breast cancer therapy. Methyl-β-cyclodextrin (MbCD), as a cholesterol depletion moiety, was conjugated to hyaluronic acid-ceramide (HACE) structure via an ester linkage. HACE-MbCD NA with 198 nm hydrodynamic size, unimodal size distribution, and spherical shape was fabricated by self-assembly strategy. By filipin III staining, it was identified that HACE-MbCD NA extracted cholesterol from the cellular membrane of MDA-MB-231 (human breast adenocarcinoma) cells more efficiently rather than MbCD and HACE NA. Efficient lipid rafts disruption of HACE-MbCD NA compared to MbCD and HACE NA groups seems to lead to the increment in apoptosis and antiproliferation efficiencies in MDA-MB-231 cells. Improvement in tumor targeting efficiency of HACE-MbCD NA compared to HACE NA in MDA-MB-231 tumor-bearing mice can be explained by the extraction process of cellular cholesterol by MbCD. Following intravenous injection in MDA-MB-231 tumor-bearing mice, the most efficient suppression of tumor growth and highest apoptotic region were observed in HACE-MbCD NA group rather than MbCD group. All of these findings suggest that CD44 receptor-targetable HACE-MbCD NA retaining cholesterol depletion activity from cancer cells may be one of the remarkable nanosystems for breast cancer therapy. Topics: Animals; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Cell Line, Tumor; Cell Proliferation; Cholesterol; Drug Delivery Systems; Female; Human Umbilical Vein Endothelial Cells; Humans; Hyaluronan Receptors; Hyaluronic Acid; Lipids; Male; Membrane Microdomains; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasm Transplantation; Neoplasms; NIH 3T3 Cells; Signal Transduction | 2018 |
Photo- and pH- Dual-Responsive β-Cyclodextrin-Based Supramolecular Prodrug Complex Self-Assemblies for Programmed Drug Delivery.
Despite the fact that progress has been made in the application of supramolecular prodrug self-assemblies to enhance the functionality of drug-delivery systems, corresponding research on multi-responsive supramolecular prodrug self-assemblies for programmed drug delivery is still limited. In this paper, the synthesis and self-assembly behavior of supramolecular prodrug complexes (SPCs) with β-cyclodextrin-acylhydrazone-doxorubicin (β-CD-hydrazone-DOX) and the targeting of azobenzene-terminated poly[2-(dimethylamino)ethyl methacrylate] (Azo-PDMA-FA) as a building block were investigated. The obtained SPCs could also form self-assemblies on the basis of their amphiphilic nature. Next, SPC-based multi-compartment vesicles and complex micelles, which were confirmed by transmission electron microscopy and dynamic/static light scattering, were obtained with good reversibility under alternative visible light or UV irradiation. Furthermore, three-stage programmed drug-delivery behavior was observed from dual-responsive SPC-based self-assemblies by utilizing UV and pH stimuli. Specifically, the SPCs first self-assembled into multicompartmental vesicles, which was accompanied by a slow release of DOX. Next, UV-light irradiation induced the dissociation of β-CD/Azo, which led to morphology transition and a slight increase in the rate of release of DOX. Upon transferring the self-assemblies to phosphate-buffer solution (pH 5.0), the release rates increased notably as a result of the broken acylhydrazone bond. Finally, basic cell experiments further demonstrated that the SPC-based self-assemblies could be internalized into cancer cells, which suggests their promise for applications in cancer therapy. Topics: Antibiotics, Antineoplastic; Azo Compounds; beta-Cyclodextrins; Cell Survival; Delayed-Action Preparations; Doxorubicin; Drug Delivery Systems; Drug Liberation; Humans; Hydrogen-Ion Concentration; MCF-7 Cells; Neoplasms; Prodrugs; Ultraviolet Rays | 2018 |
Multifunctional hetero-nanostructures of hydroxyl-rich polycation wrapped cellulose-gold hybrids for combined cancer therapy.
The development of new hetero-nanostructures for multifunctional applications in cancer therapy has attracted widespread attention. In this work, we put forward a facile approach to synthesize multifunctional hetero-nanostructures of cellulose nanocrystal (CNC)-gold nanoparticle hybrids wrapped with low-toxic hydroxyl-rich polycations to integrate versatile functions for effective cancer therapy. Biocompatible CNCs with the superior rod-like morphology for high cellular uptake were employed as substrates to flexibly load spherical gold nanoparticles (Au NPs) or gold nanorods (Au NRs) through gold-thiolate bonds, producing hetero-layered nanohybrids of CNC-Au NPs or CNC-Au NRs. Profound hydroxyl-rich cationic gene carrier, CD-PGEA (comprising β-cyclodextrin cores and ethanolamine-functionalized poly(glycidyl methacrylate) arms), was then assembled onto the surface of CNC-Au nanohybrids through host-guest interaction and gold-thiolate bonds, where PEG was employed as the intermediate and spacer. The resultant CNC-Au-PGEA hetero-nanostructures exhibited excellent performances as gene carriers. Furthermore, CNC-Au NR-PGEA comprising Au NRs demonstrated favorable optical absorption properties and were validated for photoacoustic imaging and combined photothermal/gene therapy with considerable antitumor effects. The present work provided a flexible strategy for the construction of new multifunctional hetero-nanostructures with high antitumor efficacy. Topics: Animals; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Cellulose; Combined Modality Therapy; DNA; Female; Gold; Green Fluorescent Proteins; Hydroxyl Radical; Methacrylates; Mice, Inbred BALB C; Mice, Nude; Nanostructures; Neoplasms; Photoacoustic Techniques; Phototherapy; Polyamines; Polyelectrolytes; Rats; Tumor Suppressor Protein p53 | 2017 |
Combined delivery of a TGF-β inhibitor and an adenoviral vector expressing interleukin-12 potentiates cancer immunotherapy.
Cancer immunotherapy appears to have a promising future, but it can be thwarted by secretion of immunosuppressive factors, such as transforming growth factor-β (TGF-β), which inhibits local immune responses to tumors. To weaken immune resistance of tumors and simultaneously strengthen immune responses, we developed a multifunctional polymer that could co-deliver hydrophobic TGF-β inhibitor and an adenovirus gene vector to tumor sites. This co-delivery system sustainably released TGF-β inhibitor SB-505124 and effectively transferred the adenovirus vector carrying the interleukin-12 gene. In addition, it significantly delayed growth of B16 melanoma xenografts in mice and increased animal survival. Mechanistic studies showed that this combination therapy enhanced anti-tumor immune response by activating CD4. To weaken immune resistance of tumors and simultaneously strengthen tumors' immune responses, we synthesized a structurally simple, low-toxic but functional polymer β-cyclodextrin-PEI to encapsulate a hydrophobic TGF-β inhibitor SB-505124 and to complex adenovirus vectors expressing IL-12. This is the first report demonstrating that combining TGF-β inhibitor with IL-12 could provide effective immunotherapy against melanoma by the sustainable release of SB-505124 and the effectible transduction of IL-12 gene in tumor cells. The rational delivery system presented a comprehensive and valued platform to be a candidate vector for co-delivering hydrophobic small-molecule drugs and therapeutic genes for treating cancer, providing a new approach for cancer immunotherapy. Topics: Adenoviridae; Animals; Antineoplastic Agents; Benzodioxoles; beta-Cyclodextrins; Cell Line, Tumor; Cell Movement; Combined Modality Therapy; Drug Delivery Systems; Female; Genetic Vectors; Imidazoles; Immunotherapy; Interleukin-12; Melanoma, Experimental; Mice, Inbred C57BL; Neoplasm Invasiveness; Neoplasms; Polyethyleneimine; Pyridines; Transduction, Genetic; Transforming Growth Factor beta | 2017 |
The alteration of temoporfin distribution in multicellular tumor spheroids by β-cyclodextrins.
To be effective anticancer drugs must penetrate tissue efficiently, reaching all target population of cancer cells in a concentration sufficient to exert a therapeutic effect. This study aimed to investigate the ability of methyl-β-cyclodextrin (Me-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) to alter the penetration and diffusion of temoporfin (mTHPC) in HT29 multicellular tumor spheroids. mTHPC had а nonhomogenous distribution only on the periphery of spheroids. The presence of β-CDs significantly altered the distribution of mTHPC consisting in the increase of both the depth of photosensitizer penetration and accumulation in HT29 spheroids. We suggest that this improvement is related to the nanoshuttle mechanism of β-CD action, when β-CDs facilitate mTHPC transportation to the cells in the inner layers of spheroids. As a result of mTHPC distribution improvement, β-CDs enhance mTHPC photosensitizing activity towards HT29 multicellular tumor spheroids. The observed effects strongly depend on the type of β-CD. Thus, varying the type of β-CD we can finely tune the possibility of using mTHPC for diagnostic (delimitation of tumor margins) or therapeutic purposes. Topics: 2-Hydroxypropyl-beta-cyclodextrin; beta-Cyclodextrins; Drug Carriers; HT29 Cells; Humans; Mesoporphyrins; Neoplasms; Spheroids, Cellular | 2017 |
Immobilization of β-Cyclodextrin-Conjugated Lactoferrin onto Polymer Monolith for Enrichment of Ga in Metabolic Residues of Ga-Based Anticancer Drugs.
Biological-material-functionalized porous monoliths were prepared with lactoferrin and β-cyclodextrin via a click reaction. With the monolith as an extraction medium, a method combined with ICP-MS was developed for the determination of total gallium originating from metabolic residues of orally bioavailable gallium complexes with tris(8-quinolinolato)gallium (GaQ Topics: Antineoplastic Agents; beta-Cyclodextrins; Gallium; Humans; Lactoferrin; Limit of Detection; Neoplasms; Organometallic Compounds; Oxyquinoline; Polymers; Porosity | 2017 |
Thermoresponsive supramolecular micellar drug delivery system based on star-linear pseudo-block polymer consisting of β-cyclodextrin-poly(N-isopropylacrylamide) and adamantyl-poly(ethylene glycol).
Topics: Acrylic Resins; Adamantane; Antibiotics, Antineoplastic; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Delayed-Action Preparations; Doxorubicin; Humans; Micelles; Neoplasms; Polyethylene Glycols; Temperature | 2017 |
Preparation, characterisation and antitumour activity of β-, γ- and HP-β-cyclodextrin inclusion complexes of oxaliplatin.
Three water-soluble oxaliplatin complexes were prepared by inclusion complexation with β-cyclodextrin (β-CD), γ-CD and HP-β-CD. The structures of oxaliplatin/CDs were confirmed by NMR, FTIR, TGA, XRD as well as SEM analysis. The results show that the water solubility of oxaliplatin was increased in the complex with CDs in 1:1 stoichiometry inclusion modes, and the cyclohexane ring of oxaliplatin molecule was deeply inserted into the cavity of CDs. Moreover, the stoichiometry was established by a Job plot and the water stability constant (Kc) of oxaliplatin/CDs was calculated by phase solubility studies, all results show that the oxaliplatin/β-CD complex is more stable than free oxaliplatin, oxaliplatin/HP-β-CD and oxaliplatin/γ-CD. Meanwhile, the inclusion complexes displayed almost twice as high cytotoxicity compared to free oxaliplatin against HCT116 and MCF-7 cells. This satisfactory water solubility and higher cytotoxic activity of the oxaliplatin/CD complexes will potentially be useful for their application in anti-tumour therapy. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Antineoplastic Agents; beta-Cyclodextrins; Cell Survival; Drug Carriers; gamma-Cyclodextrins; HCT116 Cells; Humans; MCF-7 Cells; Models, Molecular; Neoplasms; Organoplatinum Compounds; Oxaliplatin; Solubility; Water | 2016 |
Design and Synthesis of Core-Shell-Shell Upconversion Nanoparticles for NIR-Induced Drug Release, Photodynamic Therapy, and Cell Imaging.
Novel core-shell-shell structured nanoparticles 75 nm in diameter with all-in-one "smart" functional capabilities for simultaneous photoresponsive drug release, photodynamic therapy, and cell imaging are designed and prepared. These nanoparticles consist of an upconversion (UC) emission core, a photosensitizer-embodied silica sandwich shell, and a β-cyclodextrin (β-CD) gated mesoporous silica outmost shell with drugs (Rhodamine B as a model) loaded inside. We show in this proof-of-concept demonstration that, under 980 nm near-infrared irradiation, UC 540 nm green light emissions were emitted for cell imaging, and 660 nm red light emissions were excited for activating photosensitizers to generate singlet oxygen, which could be exploited directly to kill cancer cells and simultaneously dissociate β-CD gatekeeper to release drugs. The preliminary results reported here will shed new light on the future design and applications of multifunctional platforms for cancer therapy and diagnostic. Topics: beta-Cyclodextrins; Drug Liberation; HeLa Cells; Humans; Infrared Rays; Molecular Imaging; Nanoparticles; Neoplasms; Photochemotherapy; Rhodamines; Singlet Oxygen | 2016 |
Tunable release of chemotherapeutic and vascular disrupting agents from injectable fiber fragments potentiates combination chemotherapy.
Cancer progression and metastasis relies much on vasculature networks in tumor microenvironment, and the combination treatment with chemotherapeutic drugs and vascular disrupting agents represents apparent clinical benefits. In the current study, fiber fragments with loadings of hydroxycamptothecin (HCPT) or combretastatin A-4 (CA4) were proposed for tumor inhibition and blood vessel disruption after local administration in tumors. To address challenges in balancing the disruption of tumor vessels and intratumoral uptake of chemotherapeutic agents, this study is focus on release tuning of HCPT and CA4 from the fiber fragment mixtures. Hydroxypropyl-β-cyclodextrin (HPCD) was blended at ratios from 0 to 10% into CA4-loaded fiber fragments (Fc) to modulate CA4 release durations from 0.5 to 24days, and HCPT-loaded fiber fragments (Fh) indicated a sustained release for over 35days. In vitro cytotoxicity tests indicated a sequential inhibition on the endothelial and tumor cell growth, and the growth inhibition of tumor cells was more significant after treatment with mixtures of Fh and Fc containing 2% HPCD (Fc2) than that of other mixtures. In an orthotopic breast tumor model, compared with those of free CA4, or Fc with a fast or slow release of CA4, Fh/Fc mixtures with CA4 release durations from 2 to 12days indicated a lower tumor growth rate, a prolonged animal survival, a lower vessel density in tumors, and a less significant tumor metastasis. In addition, the tumor cell proliferation rate, hypoxia-inducible factor-1α expression within tumors, and the number of surface metastatic nodules in lungs were significantly lower after treatment with Fh/Fc2 mixtures with a CA4 release duration of 5days than those of other mixtures. It demonstrates the advantages of fiber fragment mixtures in independently modulating the release of multiple drugs and the essential role of release tuning of chemotherapeutic drugs and vascular disrupting agents in improving the therapeutic efficacy. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Angiogenesis Inhibitors; Animals; Antineoplastic Agents; beta-Cyclodextrins; Bibenzyls; Camptothecin; Cell Line, Tumor; Cell Proliferation; Drug Liberation; Drug Therapy, Combination; Female; Humans; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Mice, Inbred BALB C; Neoplasms; Tumor Microenvironment | 2016 |
Investigation of the Sequential Actions of Doxorubicin and p53 on Tumor Cell Growth Via Branched Polyethylenimine-β-cyclodextrin Conjugates.
The combination of gene therapy and chemotherapy has showed increased therapeutic efficacy in the treatment of cancers, but it is not well investigated about the actual coordination pattern between therapeutic gene and chemical drug. In this work, p53/BPEI-β-CD/AD-dox complex was fabricated and employed to investigate the interaction manner between p53 and doxorubicin (Dox). Briefly, branched polyethylenimine (BPEI) was conjugated with β-cyclodextrin hydrate (β-CD) to form BPEI-β-CD backbone, and p53 plasmid was condensed by positively charged BPEI via electrostatic interaction, while Dox was first conjugated with adamantine (AD) and then assembled with BPEI-β-CD backbone via the host-guest interaction. It was found that the BPEI-β-CD backbone possessed high endocytosis efficiency but low cytotoxicity. Moreover, p53/BPEI-β-CD/AD-dox complex released Dox and enabled the expression of p53 gene in a sequential manner, and the released Dox and expressed p53 gene showed successive inhibition of the growth of HeLa cells in vitro. With the ability to co-deliver chemical drug and therapeutic gene and exert their inhibitory actions on tumor cell growth in a sequential manner, this DNA/BPEI-β-CD/AD-drug complex via electrostatic interaction and host-guest assembly not only achieved long-term efficacy in inhibiting tumor cell growth but also can be employed as a platform to investigate the coordination pattern between chemical drugs and therapeutic genes for other purposes. Topics: beta-Cyclodextrins; Doxorubicin; Drug Carriers; Endocytosis; Gene Expression Regulation, Neoplastic; Genetic Therapy; HeLa Cells; Humans; Neoplasms; Polyethyleneimine; Tumor Suppressor Protein p53 | 2016 |
Inclusion complexation with β-cyclodextrin derivatives alters photodynamic activity and biodistribution of meta-tetra(hydroxyphenyl)chlorin.
Application of meta-tetra(hydroxyphenyl)chorin (mTHPC) one of the most effective photosensitizer (PS) in photodynamic therapy of solid tumors encounters several complications resulting from its insolubility in aqueous medium. To improve its solubility and pharmacokinetic properties, two modified β-cyclodextrins (β-CDs) methyl-β-cyclodextrin (M-β-CD) and 2-hydroxypropyl-β-cyclodextrin (Hp-β-CD) were proposed. The aim of this work was to evaluate the effect of β-CDs on mTHPC behavior at various stages of its distribution in vitro and in vivo. For this purpose, we have studied the influence of the β-CDs on mTHPC binding to the serum proteins, its accumulation, distribution and photodynamic efficiency in HT29 cells. In addition, the processes of mTHPC biodistribution in HT29 tumor bearing mice after intravenous injection of PS alone or with the β-CDs were compared. Interaction of mTHPC with studied β-CDs leads to the formation of inclusion complexes that completely abolishes its aggregation after introduction into serum. It was demonstrated that the β-CDs have a concentration-dependent effect on the process of mTHPC distribution in blood serum. At high concentrations, β-CDs can form inclusion complexes with mTHPC in the blood that can have a significant impact on PS distribution out of the vascular system in solid tissues. Besides, the β-CDs increase diffusion movement of mTHPC molecules that can significantly accelerate the delivery of PS to the targets cells and tissues. In vivo study confirms the fact that the use of β-CDs allows to modify mTHPC distribution processes in tumor bearing animals that is reflected in the decreased level of PS accumulation in skin and muscles, as well as in the increased PS accumulation in tumor. Further studies are underway to verify the optimal protocols of mTHPC/β-CD formulation for photodynamic therapy. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; beta-Cyclodextrins; Blood Proteins; Female; HT29 Cells; Humans; Kidney; Liver; Mesoporphyrins; Mice; Muscles; Neoplasms; Photochemotherapy; Photosensitizing Agents; Skin | 2016 |
Alpha- and Beta-Cyclodextrin Inclusion Complexes with 5-Fluorouracil: Characterization and Cytotoxic Activity Evaluation.
Cyclodextrins are natural macrocyclic oligosaccharides able to form inclusion complexes with a wide variety of guests, affecting their physicochemical and pharmaceutical properties. In order to obtain an improvement of the bioavailability and solubility of 5-fluorouracil, a pyrimidine analogue used as chemotherapeutic agent in the treatment of the colon, liver, and stomac cancers, the drug was complexed with alpha- and beta-cyclodextrin. The inclusion complexes were prepared in the solid state by kneading method and characterized by Fourier transform-infrared (FT-IR) spectroscopy and X-ray powder diffractometry. In solution, the 1:1 stoichiometry for all the inclusion complexes was established by the Job plot method and the binding constants were determined at different pHs by UV-VIS titration. Furthermore, the cytotoxic activity of 5-fluorouracil and its complexation products were evaluated using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay on MCF-7 (breast cancer cell line), Hep G2 (hepatocyte carcinoma cell line), Caco-2 (colon adenocarcinoma cell line), and A-549 (alveolar basal epithelial carcinoma cell line). The results showed that both inclusion complexes increased the 5-fluorouracil capability of inhibiting cell growth. In particular, 5-fluorouracil complexed with beta-cyclodextrin had the highest cytotoxic activity on MCF-7; with alpha-cyclodextrin the highest cytotoxic activity was observed on A-549. The IC Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Caco-2 Cells; Fluorouracil; Hep G2 Cells; Humans; MCF-7 Cells; Neoplasms | 2016 |
Stealth CD44-targeted hyaluronic acid supramolecular nanoassemblies for doxorubicin delivery: probing the effect of uncovalent pegylation degree on cellular uptake and blood long circulation.
Stealth active targeting nanoparticles (NPs) usually include two types of ligand sites: ligand anchored on distal ends of the polyethylene glycol (PEG) and ligand buried under pegylated layer. The latter typical case is hyaluronic acid (HA)-based NPs; however, there is little information available for the latter NPs about effect of the optimal density of surface PEG coating on the blood circulation time, cellular uptake and in vivo anticancer activity. Thus, in this study, in order to optimize the anticancer effects of HA-based NPs, we focus on how uncovalent pegylation degree modulates blood circulation time and cellular uptake of HA-based NPs. We firstly designed a new double-hydrophilic copolymer by conjugating HP-β-cyclodextrin with HA, and this carrier was further pegylated with adamantyl-peg (ADA-PEG) to form inclusion complex HA-HPCD/ADA-PEG, termed as HCPs. The supramolecular nanoassemblies were fabricated by host-guest and polar interactions between HCPs and doxorubicin (Dox), with vitamin E succinate (VES) being a nanobridge. Despite the active recognition between HA and CD44 receptor, the cellular uptake and targeting efficiency of HA-NPs decreased with the increasing peg density, demonstrating HA was partly buried by high density peg coating. However, the high density of peg coating was beneficial to long circulation time, tumor biodistribution and anticancer activity in vivo. NPs with 5% peg coating had the optimal cellular targeting efficiency in vitro and anticancer effects in vivo. The findings suggest that balancing long circulation property and cellular uptake is important to achieve the optimal antitumor efficacy for pegylated HA-based NPs, and that PEG coating densities cannot be extended beyond a certain density for shielding effect without compromising the efficacy of hyaluronic acid targeted delivery. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antibiotics, Antineoplastic; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Humans; Hyaluronan Receptors; Hyaluronic Acid; Male; Mice; Mice, Inbred BALB C; Nanoparticles; Neoplasms; Polyethylene Glycols; Rats, Sprague-Dawley; Topoisomerase II Inhibitors; Tumor Burden | 2015 |
Encapsulation of carvacrol, a monoterpene present in the essential oil of oregano, with β-cyclodextrin, improves the pharmacological response on cancer pain experimental protocols.
Cancer pain is a major public health problem worldwide due to the strong impact on the quality of life of patients and side effects of the existing therapeutic options. Monoterpenes, as carvacrol (CARV), have been extensively studied about their therapeutic properties, especially their importance in the control of painful conditions and inflammation, which can be improved through the use of inclusion complexes of β-cyclodextrin (β-CD). We evaluated the effect of encapsulation of CARV in β-CD (CARV/β-CD) on the nociception induced by tumor cells (Sarcoma 180) in rodents. Inclusion complexes were prepared in two different procedures and characterized through thermal analysis and scanning electron microscopy. CARV/β-CD complex was administered (50 mg/kg, p.o.) in mice with tumor on the hind paw and was able to reduce the hyperalgesia (von Frey) during 24 h, unlike the free CARV (100 mg/kg, p.o.), which promoted effects until 9 h. Administration on alternate days of complex of CARV/β-CD (12.5-50 mg/kg, p.o.) reduced hyperalgesia, as well as spontaneous and palpation-induced nociception. However, pure CARV (50 mg/kg) did not cause significant changes in nociceptive responses. Together, these results produced evidence that the encapsulation of carvacrol in β-cyclodextrin can be useful for the development of new options for pain management. Topics: Animals; Behavior, Animal; beta-Cyclodextrins; Calorimetry, Differential Scanning; Chemistry, Pharmaceutical; Cymenes; Hyperalgesia; Male; Mice; Monoterpenes; Neoplasms; Nociception; Oils, Volatile; Origanum; Pain; Palpation | 2015 |
Revealing the carbohydrate pattern on a cell surface by super-resolution imaging.
Carbohydrates are involved in various physiological and pathological activities including cell adhesion, signal transduction and tumor invasion. The distribution of carbohydrates is the molecular basis of their multiple functions, but remains poorly understood. Here, we employed direct stochastic optical reconstruction microscopy (dSTORM) to visualize the pattern of N-acetylglucosamine (N-GlcNAc) on Vero cell membranes at the nanometer level of resolution. We found that N-GlcNAcs exist in irregular clusters on the apical membrane with an average cluster area of about 0.37 μm(2). Most of these N-GlcNAc clusters are co-localized with lipid rafts by dual-color dSTORM imaging, suggesting that carbohydrates are closely associated with lipid rafts as the functional domains. Our results demonstrate that super-resolution imaging is capable of characterizing the distribution of carbohydrates on the cellular surface at the molecular level. Topics: Animals; beta-Cyclodextrins; Carbohydrates; Cell Adhesion; Cell Membrane; Chlorocebus aethiops; Fluorescent Dyes; Glycocalyx; Glycolipids; Glycoproteins; Membrane Microdomains; Microscopy; Microscopy, Fluorescence; Neoplasms; Optics and Photonics; Signal Transduction; Software; Vero Cells | 2015 |
Fabrication of biodendrimeric β-cyclodextrin via click reaction with potency of anticancer drug delivery agent.
The aim of this work was the synthesis of biodendrimeric β-cyclodextrin (β-CD) on the secondary face with encapsulation efficacy, with β-CDs moiety to preserve the biocompatibility properties, also particularly growth their loading capacity for drugs with certain size. The new dendrimer, having 14 β-CD residues attached to the core β-CD in secondary face (11), was prepared through click reaction. The encapsulation property of the prepared compound was evaluated by methotrexate (MTX) drug molecule. Characterization of compound 11 was performed with (1)H NMR, (13)C NMR and FTIR and its supramolecular inclusion complex structure was determined using FTIR, DLS, DSC and SEM techniques. In vitro cytotoxicity test results showed that compound 11 has very low or no cytotoxic effect on T47D cancer cells. In vitro drug release study at pHs 3, 5 and 7.4 showed that the release process was noticeably pH dependent and the dendrimer could be used as an appropriate controlled drug delivery system (DDS) for cancer treatment. Topics: Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Click Chemistry; Dendrimers; Drug Delivery Systems; Humans; Methotrexate; Neoplasms | 2015 |
Supramolecular Fluorescent Nanoparticles Constructed via Multiple Non-Covalent Interactions for the Detection of Hydrogen Peroxide in Cancer Cells.
Overabundance of hydrogen peroxide originating from environmental stress and/or genetic mutation can lead to pathological conditions. Thus, the highly sensitive detection of H2 O2 is important. Herein, supramolecular fluorescent nanoparticles self-assembled from fluorescein isothiocyanate modified β-cyclodextrin (FITC-β-CD)/rhodamine B modified ferrocene (Fc-RB) amphiphile were prepared through host-guest interaction between FITC-β-CD host and Fc-RB guest for H2 O2 detection in cancer cells. The self-assembled nanoparticles based on a combination of multiple non-covalent interactions in aqueous medium showed high sensitivity to H2 O2 while maintaining stability under physiological condition. Owing to the fluorescence resonance energy transfer (FRET) effect, addition of H2 O2 led to obvious fluorescence change of nanoparticles from red (RB) to green (FITC) in fluorescent experiments. In vitro study showed the fluorescent nanoparticles could be efficiently internalized by cancer cells and then disrupted by endogenous H2 O2 , accompanying with FRET from "on" to "off". These supramolecular fluorescent nanoparticles constructed via multiple non-covalent interactions are expected to have potential applications in diagnosis and imaging of diseases caused by oxidative stresses. Topics: beta-Cyclodextrins; Fluorescein-5-isothiocyanate; Fluorescence; Fluorescence Resonance Energy Transfer; Fluorescent Dyes; Humans; Hydrogen Peroxide; Molecular Imaging; Nanoparticles; Neoplasms; Spectrometry, Fluorescence; Thiocyanates; Water | 2015 |
Strategy to enhance efficacy of doxorubicin in solid tumor cells by methyl-β-cyclodextrin: Involvement of p53 and Fas receptor ligand complex.
Doxorubicin (DOX) is one of the preferred drugs for treating breast and liver cancers. However, its clinical application is limited due to severe side effects and the accompanying drug resistance. In this context, we investigated the effect on therapeutic efficacy of DOX by cholesterol depleting agent methyl-β-cyclodextrin (MCD), and explored the involvement of p53. MCD sensitizes MCF-7 and Hepa1-6 cells to DOX, Combination of MCD and marginal dose of DOX reduces the cell viability, and promoted apoptosis through induction of pro-apoptotic protein, Bax, activation of caspase-8 and caspase-7, down regulation of anti-apoptotic protein Bcl-2 and finally promoting PARP cleavage. Mechanistically, sensitization to DOX by MCD was due to the induction of FasR/FasL pathway through p53 activation. Furthermore, inhibition of p53 by pharmacological inhibitor pifithrin-α (PFT-α) or its specific siRNA attenuated p53 function and down-regulated FasR/FasL, thereby preventing cell death. Animal experiments were performed using C57BL/6J mouse isografted with Hepa1-6 cells. Tumor growth was retarded and survival increased in mice administered MCD together with DOX to as compared to either agent alone. Collectively, these results suggest that MCD enhances the sensitivity to DOX for which wild type p53 is an important determinant. Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Enzyme-Linked Immunosorbent Assay; Fas Ligand Protein; fas Receptor; Humans; Immunohistochemistry; Male; MCF-7 Cells; Mice; Mice, Inbred C57BL; Neoplasms; RNA Interference; RNA, Small Interfering; Survival Rate; Transplantation, Heterologous; Tumor Suppressor Protein p53 | 2015 |
Supramolecular Peptide/Surface Assembly for Monitoring Proteinase Activity and Cancer Diagnosis.
Matrix metalloproteinases (MMP) are a family of proteolytic enzymes, the expression of which in a key step of tumor progression has recently been better defined. The overexpression of one or more MMPs is thus common among malignant tumors. It may characterize tumor progression and help predict its response to chemotherapy. Consequently, the development of a device for measuring MMP activities is an important challenge for diagnosis and prognosis. In this study, we describe an innovative supramolecular peptide/surface assembly for screening MMP activities. This sensor was used to discriminate various MMP activities and to distinguish between invasive and noninvasive cancerous cell suspensions. Our results confirm the proof-of-concept of a powerful tool for the determination of the tumor aggressiveness and a technical building block for future development of MMP lab-on-chip devices. Topics: Amino Acid Sequence; beta-Cyclodextrins; Cell Line, Tumor; Fluorescent Dyes; HeLa Cells; Humans; Kinetics; Lab-On-A-Chip Devices; Matrix Metalloproteinases; Microscopy, Fluorescence; Neoplasms; Peptides; Severity of Illness Index; Spectrometry, Fluorescence; Surface Properties | 2015 |
Synthesis of the dendritic type β-cyclodextrin on primary face via click reaction applicable as drug nanocarrier.
The objective of this study was the syntheses of well-defined glycodendrimer with entrapment efficiency by click reactions, with β-cyclodextrins (β-CDs) moiety to keep the biocompatibility properties, besides especially increase their capacity to load numerous appropriate sized guests. The original dendrimer containing β-CD in both periphery and central was synthesized using click reaction. The entrapment property of the β-CD-dendrimer was studied by methotrexate (MTX) drug. The chemical structure of β-CD-dendrimer was characterized by (1)H NMR, (13)C NMR and FTIR and its inclusion complex structure were investigated by SEM, DLS, DSC and FTIR techniques. The cytotoxic effect of obtained compound and its inclusion complex with MTX was analyzed using MTT test. The MTT test exhibited that the synthesized compound was not cytotoxic to the cell line considered. The in vitro drug release study turned out that the obtained β-CD dendrimer could be a suitable controlled drug delivery system for cancer treatment. Topics: Antimetabolites, Antineoplastic; beta-Cyclodextrins; Cell Line, Tumor; Click Chemistry; Delayed-Action Preparations; Dendrimers; Humans; Methotrexate; Neoplasms | 2015 |
Engineering of Biocompatible pH-Responsive Nanovehicles from Acetalated Cyclodextrins as Effective Delivery Systems for Tumor Therapy.
There is still an unmet demand for materials with excellent biocompatibility, controlled hydrolytic capability, and elegant responsiveness to chemical or physical stimuli. To engineer biocompatible materials from β-cyclodextrin (β-CD), in this study, we synthesized acetalated β-CDs (Ac-βCDs) by one-pot acetalation using 2-ethoxypropene as an acetonation reagent, which can be further processed into nanoparticles (NPs) via the emulsion technique. Ac-βCD NPs showed pH-labile hydrolysis and pH-triggered release of docetaxel (DTX) payload. Both properties were mainly dominated by the molar ratio of linear to cyclic acetal, which can be conveniently modulated by the acetalation time used for materials synthesis. Ac-βCD NPs were found to be biocompatible in both in vitro cell culture and in vivo acute toxicity evaluations following intravenous injection. In vitro cell culture experiments demonstrated that antitumor activity of DTX against both sensitive and resistant cancer cells was remarkably improved by formulation into Ac-βCD nanomedicines. In vivo antitumor study also substantiated the dramatically enhanced efficacy of DTX/Ac-βCD NPs in a melanoma-bearing nude mouse model. These studies demonstrated that NPs derived from Ac-βCDs may serve as biocompatible and effective carriers for drug delivery. Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Biocompatible Materials; Cells, Cultured; Docetaxel; Drug Carriers; Drug Delivery Systems; Hep G2 Cells; Humans; Hydrogen-Ion Concentration; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Neoplasms; Polymers; Taxoids | 2015 |
Targeting cholesterol with β-cyclodextrin sensitizes cancer cells for apoptosis.
We found that targeting cholesterol with beta-cyclodextrin (bCD) and its derivatives disrupted signal transduction between PI3K and AKT, attenuating AKT pro-survival signals. In their absence, 2-deoxyglucose (2DG) caused anti-apoptotic protein Mcll to dissociate from pro-apoptotic Bak at mitochondria. Normally Bak is sequestered by its inhibitory associations with Mcll and Bcl-xL, and only when Bak is released from both, is it free to form oligomers through which cytochrome c can escape into the cytosol. Thus an addition of a bcl-2 antagonist dissociates Bak from Bcl-xL, triggering cytochrome c release and inducing apoptosis. 2DG-bCD can also sensitize type II cancer cells for TRAIL-mediated apoptosis. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Aniline Compounds; Animals; Anticholesteremic Agents; Antimetabolites; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; beta-Cyclodextrins; Cell Line, Tumor; Crosses, Genetic; Deoxyglucose; Drug Synergism; Humans; Mice, Inbred NOD; Mice, SCID; Neoplasms; Specific Pathogen-Free Organisms; Sulfonamides; Tumor Burden; Xenograft Model Antitumor Assays | 2015 |
Polysaccharide-gold nanocluster supramolecular conjugates as a versatile platform for the targeted delivery of anticancer drugs.
Through the high affinity of the β-cyclodextrin (β-CD) cavity for adamantane moieties, novel polysaccharide-gold nanocluster supramolecular conjugates (HACD-AuNPs) were successfully constructed from gold nanoparticles (AuNPs) bearing adamantane moieties and cyclodextrin-grafted hyaluronic acid (HACD). Due to their porous structure, the supramolecular conjugates could serve as a versatile and biocompatible platform for the loading and delivery of various anticancer drugs, such as doxorubicin hydrochloride (DOX), paclitaxel (PTX), camptothecin (CPT), irinotecan hydrochloride (CPT-11), and topotecan hydrochloride (TPT), by taking advantage of the controlled association/dissociation of drug molecules from the cavities formed by the HACD skeletons and AuNPs cores as well as by harnessing the efficient targeting of cancer cells by hyaluronic acid. Significantly, the release of anticancer drugs from the drug@HACD-AuNPs system was pH-responsive, with more efficient release occurring under a mildly acidic environment, such as that in a cancer cell. Taking the anticancer drug DOX as an example, cell viability experiments revealed that the DOX@HACD-AuNPs system exhibited similar tumor cell inhibition abilities but lower toxicity than free DOX due to the hyaluronic acid reporter-mediated endocytosis. Therefore, the HACD-AuNPs supramolecular conjugates may possess great potential for the targeted delivery of anticancer drugs. Topics: Antineoplastic Agents; beta-Cyclodextrins; Cell Line, Tumor; Cell Survival; Drug Carriers; Drug Delivery Systems; Gold; Humans; Metal Nanoparticles; Neoplasms; Polysaccharides | 2014 |
Enhanced anti-cancer efficacy to cancer cells by doxorubicin loaded water-soluble amino acid-modified β-cyclodextrin platinum complexes.
The effective targeted delivery of insoluble anticancer drugs to increase the intracellular drug concentration has become a focus in cancer therapy. In this system, two water-soluble amino acid-modified β-cyclodextrin (β-CD) platinum complexes were reported. They showed preferable binding ability to DNA and effective inhibition to cancer cells, and they could bind and unwind pBR322 DNA in a manner which was similar to cisplatin. Besides, our platinum complexes could effectively deliver the anticancer drug doxorubicin (Dox) into cells and had higher cell inhibition ratio, but less toxicity on the normal cells, compared with cancer cells. In this combination system, Dox was encapsulated into the hydrophobic cavities of β-CD at the optimum molar ratio of 1:1, which were validated by UV-visible (UV-vis) absorption spectroscopy, fluorescence spectroscopy and MTT experiments. Moreover, the combination system had higher cell inhibition ratio than free Dox and amino acid-modified β-CD platinum complexes, and the results of high content screening (HCS) showed that Dox-loaded amino acid-modified β-CD platinum complexes could permeate the cell membrane and enter cells, suggesting the efficient transport of Dox across the membranes with the aid of the β-CD. We expect that the amino acid-modified β-CD platinum complexes will deliver the antitumor drug Dox to enhance intracellular drug accumulation and such combination system showed great potential as an antitumor drug. Topics: Amino Acids; beta-Cyclodextrins; Cell Line, Tumor; Doxorubicin; Drug Carriers; Humans; Hydrophobic and Hydrophilic Interactions; Neoplasms; Platinum Compounds; Water | 2014 |
Fabrication of versatile cyclodextrin-functionalized upconversion luminescence nanoplatform for biomedical imaging.
Lanthanide-based upconversion nanoparticles (UCNPs) are a new type of luminescent tags that show great application potential in biomedical fields. However, a major challenge when applying UCNPs in biomedical research is the lack of a versatile strategy to make water-dispersible and biocompatible UCNPs with high simplicity in functionalization. To address this problem, in the present work, we employed 6-phosphate-6-deoxy-β-cyclodextrin (βPCD) as the novel ligand to fabricate a versatile upconversion luminescent nanoplatform. Using βPCD as the surface ligand not only enhances the stability and biocompatibility of the UCNPs under physiological conditions but also enables simple conjugation with various functional molecules, such as organic dyes and biomolecules, via the host-guest interaction between those molecules and the cyclodextrin cavity. The conjugated upconversion nanoprobe then displays excellent capability in labeling the cancer cells and tumor tissue slices for luminescent imaging. These results demonstrate that the versatile cyclodextrin-functionalized upconversion nanoplatform appears particularly flexible for further modifications, indicating great potential for applications in biosensing and bioimaging. Topics: beta-Cyclodextrins; Cell Line, Tumor; Female; HeLa Cells; Humans; Lanthanoid Series Elements; Luminescence; Luminescent Agents; Nanoparticles; Neoplasms; Optical Imaging | 2014 |
Nanosuspension for the delivery of a poorly soluble anti-cancer kinase inhibitor.
We hypothesized that nanosuspensions could be promising for the delivery of the poorly water soluble anti-cancer multi-targeted kinase inhibitor, MTKi-327. Hence, the aims of this work were (i) to evaluate the MTKi-327 nanosuspension for parenteral and oral administrations and (ii) to compare this nanosuspension with other nanocarriers in terms of anti-cancer efficacy and pharmacokinetics. Therefore, four formulations of MTKi-327 were studied: (i) PEGylated PLGA-based nanoparticles, (ii) self-assembling PEG₇₅₀-p-(CL-co-TMC) polymeric micelles, (iii) nanosuspensions of MTKi-327; and (iv) Captisol solution (pH=3.5). All the nano-formulations presented a size below 200 nm. Injections of the highest possible dose of the three nano-formulations did not induce any side effects in mice. In contrast, the maximum tolerated dose of the control Captisol solution was 20-fold lower than its highest possible dose. The highest regrowth delay of A-431-tumor-bearing nude mice was obtained with MTKi-327 nanosuspension, administered intravenously, at a dose of 650 mg/kg. After intravenous and oral administration, the AUC₀₋∞ of MTKi-327 nanosuspension was 2.4-fold greater than that of the Captisol solution. Nanosuspension may be considered as an effective anti-cancer MTKi-327 delivery method due to (i) the higher MTKi-327 maximum tolerated dose, (ii) the possible intravenous injection of MTKi-327, (iii) its ability to enhance the administered dose and (iv) its higher efficacy. Topics: Administration, Oral; Animals; Antineoplastic Agents; Area Under Curve; beta-Cyclodextrins; Drug Delivery Systems; Drug Screening Assays, Antitumor; Humans; Hydrogen-Ion Concentration; Macrocyclic Compounds; Maximum Tolerated Dose; Mice; Mice, Nude; Micelles; Nanoparticles; Neoplasm Transplantation; Neoplasms; Polymers; Protein Kinase Inhibitors; Solubility; Suspensions | 2014 |
Intracellular redox-activated anticancer drug delivery by functionalized hollow mesoporous silica nanoreservoirs with tumor specificity.
In this study, a type of intracellular redox-triggered hollow mesoporous silica nanoreservoirs (HMSNs) with tumor specificity was developed in order to deliver anticancer drug (i.e., doxorubicin (DOX)) to the target tumor cells with high therapeutic efficiency and reduced side effects. Firstly, adamantanamine was grafted onto the orifices of HMSNs using a redox-cleavable disulfide bond as an intermediate linker. Subsequently, a synthetic functional molecule, lactobionic acid-grafted-β-cyclodextrin (β-CD-LA), was immobilized on the surface of HMSNs through specific complexation with the adamantyl group, where β-CD served as an end-capper to keep the loaded drug within HMSNs. β-CD-LA on HMSNs could also act as a targeting agent towards tumor cells (i.e., HepG2 cells), since the lactose group in β-CD-LA is a specific ligand binding with the asialoglycoprotein receptor (ASGP-R) on HepG2 cells. In vitro studies demonstrated that DOX-loaded nanoreservoirs could be selectively endocytosed by HepG2 cells, releasing therapeutic DOX into cytoplasm and efficiently inducing the apoptosis and cell death. In vivo investigations further confirmed that DOX-loaded nanoreservoirs could permeate into the tumor sites and actively interact with tumor cells, which inhibited the tumor growth with the minimized side effect. On the whole, this drug delivery system exhibits a great potential as an efficient carrier for targeted tumor therapy in vitro and in vivo. Topics: Animals; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Disaccharides; Doxorubicin; Drug Delivery Systems; Endocytosis; Hep G2 Cells; Humans; Intracellular Space; Mice, Nude; Nanoparticles; Neoplasms; Oxidation-Reduction; Porosity; Silicon Dioxide; Solutions | 2014 |
Linear poly(ethylenimine) cross-linked by methyl-β-cyclodextrin for gene delivery.
Poly(ethylenimine) (PEI) is a cationic polymer extensively exploited for non-viral gene delivery; however, its wide application has been impeded by its cytotoxicity. PEI can assume either a branched or linear configuration. Whereas branched PEI (bPEI) is more chemically reactive and can form smaller complexes with DNA under salt-containing conditions, lPEI is generally less toxic and exhibits higher transfection efficiency. In this study, we cross-linked low-molecularweight lPEI with methyl β-cyclodextrin (MβCD) to form MβCD-lPEI (MLP). The structure of MLP was successfully characterized by NMR, FT-IR, MALDI-TOF and elemental analysis. In the standard serum-free transfection environment, MLP could effectively transfect glioblastoma, melanoma and hepatocarcinoma cells. A high transfection efficiency was maintained in the presence of serum. Apart from its high transfection efficiency, MLP was found to have negligible cytotoxicity over a wide range of concentrations and to exhibit a low membrane disruptive capacity ex vivo. MLP warrants further development as a promising gene delivery system for future research. Topics: Animals; beta-Cyclodextrins; Cell Line, Tumor; Chemistry Techniques, Synthetic; Cross-Linking Reagents; Female; Gene Transfer Techniques; Genetic Therapy; Humans; Magnetic Resonance Spectroscopy; Mice, Inbred C57BL; Molecular Structure; Molecular Weight; Neoplasms; Polyethyleneimine; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; Spectroscopy, Fourier Transform Infrared; Transfection | 2014 |
Involvement of cholesterol depletion from lipid rafts in apoptosis induced by methyl-β-cyclodextrin.
Methyl-β-cyclodextrin (M-β-CyD), which is widely used as a lipid rafts disrupting agent, is known to induce cytotoxicity at high concentration. In the present study, we investigated the potential of M-β-CyD as an antitumor drug. M-β-CyD markedly caused apoptotic cell-death in KB cells, a human oral squamous carcinoma cell line, Ihara cells, a highly pigmented human melanoma cell line, and M213 cells, a human cholangiocarcinoma cell line, through cholesterol depletion in cell membranes. The DNA content and mitochondrial transmembrane potential in KB cells were significantly decreased after treatment with M-β-CyD. Additionally, M-β-CyD elevated the caspase-3/7 activity in KB cells. Meanwhile, M-β-CyD did not induce the formation of autophagic vacuoles in KB cells. M-β-CyD drastically inhibited the tumor growth after intratumoral injection to Colon-26 cells-bearing mice. These results strongly suggest that M-β-CyD induced apoptosis in tumor cells and had the potential a novel antitumor agent and/or its lead compound. Topics: Animals; Antineoplastic Agents; Apoptosis; beta-Cyclodextrins; Caspase 3; Caspase 7; Cell Line, Tumor; Cell Survival; Cholesterol; DNA; Humans; Male; Membrane Microdomains; Membrane Potential, Mitochondrial; Mice; Mice, Inbred BALB C; Neoplasms; Tumor Burden | 2013 |
Cholesterol masks membrane glycosphingolipid tumor-associated antigens to reduce their immunodetection in human cancer biopsies.
Glycosphingolipids (GSLs) are neoplastic and normal/cancer stem cell markers and GSL/cholesterol-containing membrane rafts are increased in cancer cell plasma membranes. We define a novel means by which cancer cells can restrict tumor-associated GSL immunoreactivity. The GSL-cholesterol complex reorients GSL carbohydrate to a membrane parallel, rather than perpendicular conformation, largely unavailable for antibody recognition. Methyl-β-cyclodextrin cholesterol extraction of all primary human tumor frozen sections tested (ovarian, testicular, neuroblastoma, prostate, breast, colon, pheochromocytoma and ganglioneuroma), unmasked previously "invisible" membrane GSLs for immunodetection. In ovarian carcinoma, globotriaosyl ceramide (Gb3), the GSL receptor for the antineoplastic Escherichia coli-derived verotoxin, was increased throughout the tumor. In colon carcinoma, Gb3 detection was vastly increased within the neovasculature and perivascular stroma. In tumors considered Gb3 negative (neuroblastoma, Leydig testicular tumor and pheochromocytoma), neovascular Gb3 was unmasked. Tumor-associated GSL stage-specific embryonic antigen (SSEA)-1, SSEA-3, SSEA-4 and globoH were unmasked according to tumor: SSEA-1 in prostate/colon; SSEA-3 in prostate; SSEA-4 in pheochromocytoma/some colon tumors; globoH in prostate/some colon tumors. In colon, anti-SSEA-1 was tumor cell specific. Within the GSL-cholesterol complex, filipin-cholesterol binding was also reduced. These results may relate to the ill-defined benefit of statins on cancer prognosis, for example, prostate carcinoma. We found novel anti-tumor GSL antibodies circulating in 3/5 statin-treated, but not untreated, prostate cancer patients. Lowering tumor membrane cholesterol may permit immune recognition of otherwise unavailable tumor-associated GSL carbohydrate, for more effective immunosurveillance and active/passive immunotherapy. Our results show standard immunodetection of tumor GSLs significantly under assesses tumor membrane GSL content, impinging on the current use of such antigens as cancer vaccines. Topics: Antibodies, Neoplasm; Antigens, Neoplasm; beta-Cyclodextrins; Biomarkers, Tumor; Biopsy; Cell Membrane; Cholesterol; Female; Globosides; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Immunohistochemistry; Immunotherapy; Male; Neoplasms; Stage-Specific Embryonic Antigens | 2013 |
In vivo treatment of tumors using host-guest conjugated nanoparticles functionalized with doxorubicin and therapeutic gene pTRAIL.
The combination of gene therapy and chemotherapy may increase the therapeutic efficacy in the treatment of patients. In this work, the anti-cancer drug Dox and therapeutic gene pTRAIL-loaded host-guest co-delivery system was assayed for the possibility of in vivo synergistically treating tumors. The introduced Dox could act as an auxiliary component to human tumor necrosis factor-related apoptosis-inducing ligand-encoding plasmid gene pTRAIL. Such delivery system possessed the good ability of in vivo retention of chemotherapeutic drugs, achieved good therapeutic effects in the inhibition of tumor growth and significantly prolonged the survival time of tumor-bearing mice. With the efficient ability to co-deliver drug and gene, such host-guest assembly should have great potential applications in cancer therapy. Topics: Adamantane; Animals; beta-Cyclodextrins; Cell Death; Cell Line, Tumor; Doxorubicin; Female; Flow Cytometry; Green Fluorescent Proteins; Humans; Mice; Mice, Nude; Microscopy, Confocal; Nanoparticles; Neoplasms; Plasmids; Polyethyleneimine; TNF-Related Apoptosis-Inducing Ligand | 2012 |
Antitumor activities of emulsion electrospun fibers with core loading of hydroxycamptothecin via intratumoral implantation.
Emulsion electrospinning was used in the present study to prepare core-sheath structured fibers with core-loading of hydroxycamptothecin (HCPT), and their antitumor activities were evaluated both in vitro on cancer cell lines and in vivo on tumor bearing mice via intratumoral implantation. Compared with our previous investigation on blend electrospun fibers, the addition of 2-hydroxypropyl-β-cyclodextrin (HPCD) and the preferential formation of HPCT/HPCD inclusion complexes resulted in significantly faster HCPT release from and higher degradation rate of emulsion electrospun fibers. The core-sheath structure led to around 93% of lactone form remaining after emulsion electrospinning and incubation in buffer solutions for over one month. In vitro cytotoxicity tests on HCPT-loaded electrospun fibers indicated over 20 times higher inhibitory activity against HepG2 cells than free HCPT during 72h incubation. Hepatoma H22 cells were subcutaneously injected into Kunming mice to form solid tumors for in vivo tests on the antitumor efficacy. Based on the tumor volume, survival rate and body weight changes, HCPT-loaded fibers indicated superior in vivo antitumor activities to and fewer side effects than free HCPT. The histopathological staining and immunohistochemical examinations of caspase-3 expression indicated more necrosis and apoptosis induced by HCPT-loaded fibers. The above results demonstrate the potential use of emulsion electrospun fibers as drug carriers for local treatment of solid tumors. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Animals; Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Camptothecin; Cell Line, Tumor; Cell Survival; Drug Carriers; Emulsions; Humans; Lactates; Mice; Neoplasm Transplantation; Neoplasms; Polyethylene Glycols; Tumor Burden | 2012 |
Folate-conjugated β-cyclodextrin from click chemistry strategy and for tumor-targeted drug delivery.
To enhance site-specific intracellular delivery against the folate receptor, a drug carrier was designed and synthesized by bioconjugation of folic acid (FA) to β-cyclodextrins (β-CD) through a poly(ethylene glycol) (PEG) spacer from "click chemistry" strategy. The resulted conjugates were confirmed by (1)H NMR and IR spectroscopy. Host-guest interactions between hydrophobic drug and β-CD are capable of entrapping a hydrophobic drug, like 5-Fluorouracil, to form drug-β-CD-PEG-FA nanoparticles (NPs) in aqueous solution. The morphology and size of β-CD-PEG-FA NPs were measured by transmission electron microscopy (TEM) and dynamic light scattering (DLS). The targeting ability of the β-CD-PEG-FA NPs was investigated against two kinds of cell lines (HeLa and A549), which have different amounts of folate receptors on their surface. Confocal image analysis revealed that β-CD-PEG-FA conjugate-assembled nanoparticles exhibited a greater extent of cellular uptake against HeLa cells than A549 cells. This suggests folate-receptor-mediated endocytosis can affect the cellular uptake efficiency of drug-loaded β-CD-PEG-FA NPs. The β-CD-PEG-FA conjugates that are presented may be promising active tumor-targeting carrier candidates via folate mediation. Topics: Antimetabolites, Antineoplastic; beta-Cyclodextrins; Cell Line, Tumor; Click Chemistry; Drug Carriers; Drug Delivery Systems; Endocytosis; Fluorouracil; Folic Acid; HeLa Cells; Humans; Nanoparticles; Neoplasms; Polyethylene Glycols | 2012 |
Solid lipid nanoparticles of paclitaxel strengthened by hydroxypropyl-β-cyclodextrin as an oral delivery system.
The objective of this study was to evaluate the potential of surface-modified paclitaxel (PTX)-incorporated solid lipid nanoparticles with hydroxypropyl-β-cyclodextrin (smPSH). The smPSH released 89.70 ± 3.99% of its entrapped PTX within 24 h when placed in dissolution medium containing sodium lauryl sulfate. The cellular uptake of PTX from smPSH in Caco-2 cells was 5.3-fold increased compared to a PTX solution based on a Taxol formulation. Moreover, smPSH showed an increased cytotoxicity compared to PTX solution. In addition, AUC (5.43 µg•h/ml) and Cmax (1.44 µg/ml) of smPSH were higher than those (1.81 µg•h/ml and 0.73 µg/ml) of PTX solution. The drug concentration of smPSH (11.12 ± 4.45 ng/mg of lymph tissue) in lymph nodes was higher than that of the PTX solution (0.89 ± 0.75 ng/mg of lymph tissue), suggesting that more PTX was transported to the lymphatic vessels in the form of smPSH. In conclusion, smPSH have a potential as an alternative delivery system for oral administration of PTX. Topics: 2-Hydroxypropyl-beta-cyclodextrin; Administration, Oral; Animals; Antineoplastic Agents, Phytogenic; beta-Cyclodextrins; Caco-2 Cells; Cell Survival; Drug Carriers; Humans; Male; Nanoparticles; Neoplasms; Paclitaxel; Rats; Rats, Sprague-Dawley | 2012 |
A host-guest supramolecular complex with photoregulated delivery of nitric oxide and fluorescence imaging capacity in cancer cells.
Herein we report the design, preparation, and properties of a supramolecular system based on a tailored nitric oxide (NO) photodonor and a rhodamine-labeled β-cyclodextrin conjugate. The combination of spectroscopic and photochemical experiments shows the absence of significant interchromophoric interactions between the host and the guest in the excited states. As a result, the complex is able to release NO under the exclusive control of visible light, as unambiguously demonstrated by direct detection of this transient species through an amperometric technique, and exhibits the typical red fluorescence of the rhodamine appendage. The supramolecular complex effectively internalizes in HeLa cancer cells as proven by fluorescence microscopy, shows a satisfactory biocompatibility in the dark, and induces about 50% of cell mortality upon irradiation with visible light. The convergence of all these properties in one single complex makes the present host-guest ensemble an appealing candidate for further delevopment of photoactivatable nanoscaled systems addressed to photostimulated NO-based therapy. Topics: Antineoplastic Agents; beta-Cyclodextrins; Cell Survival; Delayed-Action Preparations; HeLa Cells; Humans; Light; Neoplasms; Nitric Oxide Donors; Optical Imaging; Rhodamines | 2012 |
Multi-functional magnetic nanoparticles for magnetic resonance imaging and cancer therapy.
We have developed a multi-layer approach for the synthesis of water-dispersible superparamagnetic iron oxide nanoparticles for hyperthermia, magnetic resonance imaging (MRI) and drug delivery applications. In this approach, iron oxide core nanoparticles were obtained by precipitation of iron salts in the presence of ammonia and provided β-cyclodextrin and pluronic polymer (F127) coatings. This formulation (F127250) was highly water dispersible which allowed encapsulation of the anti-cancer drug(s) in β-cyclodextrin and pluronic polymer for sustained drug release. The F127250 formulation has exhibited superior hyperthermia effects over time under alternating magnetic field compared to pure magnetic nanoparticles (MNP) and β-cyclodextrin coated nanoparticles (CD200). Additionally, the improved MRI characteristics were also observed for the F127250 formulation in agar gel and in cisplatin resistant ovarian cancer cells (A12780CP) compared to MNP and CD200 formulations. Furthermore, the drug-loaded formulation of F127250 exhibited many folds of imaging contrast properties. Due to the internalization capacity of the F127250 formulation, its curcumin-loaded formulation (F127250-CUR) exhibited almost equivalent inhibition effects on A2780CP (ovarian), MDA-MB-231 (breast), and PC-3 (prostate) cancer cells even though curcumin release was only 40%. The improved therapeutic effects were verified by examining molecular effects using Western blotting and transmission electron microscopic (TEM) studies. F127250-CUR also exhibited haemocompatibility, suggesting a nanochemo-therapeutic agent for cancer therapy. Topics: beta-Cyclodextrins; Blotting, Western; Cell Line, Tumor; Humans; Hyperthermia, Induced; Magnetic Resonance Imaging; Magnetics; Nanoparticles; Neoplasms | 2011 |
A label-free indicator for tumor cells based on the CH2-stretch ratio.
In this paper, we assess the potential of a label-free infrared absorbance based measurement method for determination of the CH(2)-symmetric to CH(2)-antisymmetric stretch ratio, to aid in the detection of the presence of cancer cells and to differentiate between various cancer cells. For this study a normal epithelial kidney cell line, two carcinoma epithelial kidney cell lines, an adult primary human melanocyte cell line, and three human melanoma cell lines were investigated. For the measurements we used a self-designed IR sensor which has the potential to be further developed in a point-of-care instrument. To investigate the mechanism influencing the CH(2)-stretch ratio of mammalian cell membranes, a normal epithelial kidney cell line was exposed to the plasma membrane bound cholesterol reducing agent methyl-β-cyclodextrin. This methodology yielded statistically significant CH(2)-stretch ratio differences between the individual cell lines, normal and tumorous, of both epithelial kidney and melanocyte origin. Measurement results of normal epithelial kidney cells exposed to methyl-β-cyclodextrin indicate that an increase in the CH(2)-stretch ratio arises when there is a decrease in, or redistribution of, the membrane stabilizing agent cholesterol. This study proves that the proposed cell type discrimination method, based on the CH(2)-symmetric to CH(2)-antisymmetric stretch ratio, allows the discrimination between normal and tumor cells. In addition, the method shows high potential for improvement of staging of suspicious tissues. Topics: beta-Cyclodextrins; Carbon; Cell Line, Tumor; Cholesterol; Humans; Hydrogen; Neoplasms; Spectrophotometry, Infrared | 2011 |
Pharmacokinetics, efficacy, and safety evaluation of docetaxel/hydroxypropyl-sulfobutyl-β-cyclodextrin inclusion complex.
Hydroxypropyl-sulfobutyl-β-cyclodextrin (HP-SBE-β-CD) inclusion complex was developed and used as a drug delivery system for DTX (DTX/HP-SBE-β-CD). The objective of the present study was to evaluate and compare the biological properties of DTX/HP-SBE-Β-CD with Taxotere®. The pharmacokinetics, biodistribution, antitumor efficacy in vivo and in vitro, and safety evaluation of DTX/HP-SBE-β-CD were studied. The most significant finding was that it was possible to prepare a Polysorbate-80-free inclusion complex for DTX. Studies based on pharmacokinetics, biodistribution, and antitumor efficacy indicated that DTX/HP-SBE-β-CD had similar pharmacokinetic properties and antitumor efficacy both in vitro and in vivo as Taxotere®. Fortunately, this new drug delivery system attenuated the side effects when used in vivo. As a consequence, DTX/HP-SBE-β-CD may be a promising alternative to Taxotere® for cancer chemotherapy treatment with reduced side effects. The therapeutic potential against a variety of human tumors and low toxicity demonstrated in a stringent study clearly warrant clinical investigation of DTX/HP-SBE-β-CD for possible use against human tumors. Topics: Animals; beta-Cyclodextrins; Docetaxel; Drug Delivery Systems; HCT116 Cells; Hep G2 Cells; Humans; Male; Mice; Neoplasms; Rabbits; Random Allocation; Rats; Rats, Wistar; Taxoids; Treatment Outcome; Xenograft Model Antitumor Assays | 2011 |
An active endocytosis pathway is required for the cytotoxic effects of glycosylated antitumor ether lipids.
Glycosylated antitumor ether lipids (GAELs) kill cells by an apoptosis-independent pathway. A hallmark of this pathway is the formation of large acidic vacuoles; however, very little is known about the process. We examined the hypothesis that 1-O-hexadecyl-2-O-methyl-3-O-(2'-amino-2'-deoxy-β-D-glucopyranosyl)-sn-glycerol (Gln), a potent GAEL, diffuses across cell membranes into lysosomes, where protonation of the amine leads to its accumulation and generation of the vacuoles.. N-Benzylamine analogs with similar pKa values, but with greater hydrophobicity than the parental Gln were synthesized and their activities against epithelial cancer cell lines were compared. The role of endocytosis in Gln action was investigated by inhibiting endocytosis with methyl-β-cyclodextrin (MCD), and inhibiting the maturation of the endocytic vesicles by low temperature incubation and analyzing their effects on Gln activity.. The N-benzylamines were either inactive or less active than Gln, indicating that activity was unrelated to diffusion or protonation. Toxicity was only observed with analogs that generated vacuoles. The incubation of cells with MCD inhibited the generation of the vacuoles and the toxic effects of Gln. The toxic effect of Gln was inhibited when cells were incubated with the drug at 20°C, a temperature that inhibits the maturation of early endosomes.. The results of the study show that GAELs are taken up by endocytosis and an active endocytic pathway is required for the formation of large acidic vacuoles by GAELs and manifestation of their cytotoxic effects. Topics: Animals; Antineoplastic Agents; beta-Cyclodextrins; Cell Proliferation; Cells, Cultured; Endocytosis; Glycolipids; Glycosylation; Humans; Lysosomes; MAP Kinase Kinase Kinase 5; Mice; Mice, Knockout; Neoplasms; Vacuoles | 2011 |
Hsp60 is actively secreted by human tumor cells.
Hsp60, a Group I mitochondrial chaperonin, is classically considered an intracellular chaperone with residence in the mitochondria; nonetheless, in the last few years it has been found extracellularly as well as in the cell membrane. Important questions remain pertaining to extracellular Hsp60 such as how generalized is its occurrence outside cells, what are its extracellular functions and the translocation mechanisms that transport the chaperone outside of the cell. These questions are particularly relevant for cancer biology since it is believed that extracellular chaperones, like Hsp70, may play an active role in tumor growth and dissemination.. Since cancer cells may undergo necrosis and apoptosis, it could be possible that extracellular Hsps are chiefly the result of cell destruction but not the product of an active, physiological process. In this work, we studied three tumor cells lines and found that they all release Hsp60 into the culture media by an active mechanism independently of cell death. Biochemical analyses of one of the cell lines revealed that Hsp60 secretion was significantly reduced, by inhibitors of exosomes and lipid rafts.. Our data suggest that Hsp60 release is the result of an active secretion mechanism and, since extracellular release of the chaperone was demonstrated in all tumor cell lines investigated, our observations most likely reflect a general physiological phenomenon, occurring in many tumors. Topics: Acetylcholinesterase; Amiloride; Apoptosis; beta-Cyclodextrins; Blotting, Western; Cell Line; Cell Line, Tumor; Cell Survival; Chaperonin 60; Culture Media, Conditioned; Exosomes; Extracellular Space; Humans; K562 Cells; Microscopy, Electron, Transmission; Neoplasms | 2010 |
Core-shell nanosized assemblies mediated by the alpha-beta cyclodextrin dimer with a tumor-triggered targeting property.
In this paper, the alpha-beta cyclodextrin dimer is designed via "click" chemistry to connect the hydrophilic and hydrophobic segments to form self-assembled noncovalently connected micelles (NCCMs) through host-guest interactions. A peptide containing the Arg-Gly-Asp (RGD) sequence was introduced to NCCMs as a target ligand to improve the cell uptake efficacy, while PEGylated technology was employed via benzoic-imine bonds to protect the ligands in normal tissues and body fluid. In addition, two fluorescent dyes were conjugated to different segments to track the formation of the micelles as well as the assemblies. It was found that the targeting property of NCCMs was switched off before reaching the tumor sites and switched on after removing the poly(ethylene glycol) (PEG) segment in the tumor sites, which was called "tumor-triggered targeting". With deshielding of the PEG segment, the drugs loaded in NCCMs could be released rapidly due to the thermoinduced phase transition. The new concept of "tumor-triggered targeting" proposed here has great potential for cancer treatment. Topics: alpha-Cyclodextrins; beta-Cyclodextrins; Cell Survival; Dimerization; Doxorubicin; Drug Carriers; Fluorescein-5-isothiocyanate; Fluorescent Dyes; HeLa Cells; Humans; Hydrophobic and Hydrophilic Interactions; Micelles; Nanoshells; Neoplasms; Oligopeptides; Polyethylene Glycols; Rhodamines | 2010 |
Highly sensitive identification of cancer cells by combining the new tetrathiafulvalene derivative with a β-cyclodextrin/multi-walled carbon nanotubes modified GCE.
In this contribution, we have prepared and explored a novel nano-interface based probe for the rapid identification and highly sensitive detection of cancer cells by means of an electrochemical study. The new probe tetrathiafulvalene (TTF) carboxylate salt (TTF-(COONBu(4))(2), ditetrabutylammonium salt for propylenedithio-4',5'-tetrathiafulvalene-4,5-dicarboxylate), which has specific spectral and electrochemical properties, has been synthesized and assembled with carbon nanotubes to form a new type of nanocomposite. A simple method of fabricating the β-CD/MWCNT modified electrodes based on functionalized multi-walled carbon nanotubes (MWCNTs) and β-cyclodextrin (β-CD) has been explored by using glassy carbon electrodes (GCEs), which could remarkably enhance the sensitivity of the biomolecular detection. Our results demonstrate that the combination of the new probe TTF-(COONBu(4))(2) with β-CD/MWCNT modified electrodes could be readily utilized to sensitively detect cancer cells such as liver cancer cells SMMC-7721 and HepG2, drug sensitive leukemia K562/B.W cells and drug resistant leukemia K562/ADM cells, with a detection limit of ~10(3) cells mL(-1). This may provide a novel strategy for the potential and promising application of the new TTF molecular probe in the development of multi-signal responsive biosensors for the early diagnosis of cancers. Topics: beta-Cyclodextrins; Carbon; Cells, Cultured; Electrochemistry; Electrodes; Glass; Heterocyclic Compounds, 1-Ring; Humans; Molecular Structure; Nanotubes, Carbon; Neoplasms; Particle Size; Sensitivity and Specificity; Stereoisomerism; Surface Properties | 2010 |
Metabonomics study on the effects of the ginsenoside Rg3 in a beta-cyclodextrin-based formulation on tumor-bearing rats by a fully automatic hydrophilic interaction/reversed-phase column-switching HPLC-ESI-MS approach.
The goal of this study was the application of a novel, fully automatic column-switching approach in a metabonomics study combining the orthogonal selectivities of hydrophilic interaction chromatography (HILIC) and reversed-phase chromatography. The temporal, pharmacodynamic effects of the ginsenoside Rg3 on the metabonome in urine of healthy and liver-tumor-bearing rats have been investigated. Within a total analysis time of 52 min we detected 5686 polar, and on the second column an additional 1808 apolar, urinary metabolite ions. The administration of a single, high dose of Rg3 in a beta-cyclodextrin-based formulation led to a considerable change of the metabolic pattern in cancer rats during 3 days studied. Seventeen biomarker candidates including three apolar metabolites, which were not retained on the HILIC column, were detected. Overall, the results suggest that the developed liquid chromatography-mass spectrometry strategy is a promising tool in metabonomics studies for global analysis of highly complex biosamples. It may not only increase the number of discovered biomarkers but consequently improve the comprehensive information on metabolic changes in a fully automatic manner. Topics: Animals; beta-Cyclodextrins; Biomarkers; Cell Line, Tumor; Chromatography, High Pressure Liquid; Ginsenosides; Glycomics; Health; Hydrophobic and Hydrophilic Interactions; Male; Molecular Structure; Neoplasms; Rats; Rats, Sprague-Dawley; Spectrometry, Mass, Electrospray Ionization | 2008 |
Elevated levels of cholesterol-rich lipid rafts in cancer cells are correlated with apoptosis sensitivity induced by cholesterol-depleting agents.
Lipid rafts/caveolae are membrane platforms for signaling molecules that regulate various cellular functions, including cell survival. To better understand the role of rafts in tumor progression and therapeutics, we investigated the effect of raft disruption on cell viability and compared raft levels in human cancer cell lines versus their normal counterparts. Here, we report that cholesterol depletion using methyl-beta cyclodextrin caused anoikis-like apoptosis, which in A431 cells involved decreased raft levels, Bcl-xL down-regulation, caspase-3 activation, and Akt inactivation regardless of epidermal growth factor receptor activation. Cholesterol repletion replenished rafts on the cell surface and restored Akt activation and cell viability. Moreover, the breast cancer and the prostate cancer cell lines contained more lipid rafts and were more sensitive to cholesterol depletion-induced cell death than their normal counterparts. These results indicate that cancer cells contain increased levels of rafts and suggest a potential use of raft-modulating agents as anti-cancer drugs. Topics: Apoptosis; bcl-X Protein; beta-Cyclodextrins; Breast Neoplasms; Carcinoma, Squamous Cell; Caspase 3; Caspases; Cell Line, Tumor; Cell Survival; Cholesterol; Down-Regulation; Enzyme Activation; ErbB Receptors; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Membrane Microdomains; Neoplasms; Prostatic Neoplasms; Proto-Oncogene Proteins c-akt; Signal Transduction; Simvastatin | 2006 |
EXPERIMENTAL RESULTS FROM EXPOSURE OF CLOUDMAN S-91 MELANOMA IN THE CDBA/2F1 HYBRID MOUSE TO NEODYMIUM OR RUBY LASER RADIATION.
Topics: Animals; Benzaldehydes; beta-Cyclodextrins; Lasers; Lasers, Solid-State; Melanoma; Mice; Neodymium; Neoplasms; Neoplasms, Experimental; Radiation Effects; Research | 1965 |
THE EFFECT OF RUBY LASER RADIATION ON THE CLOUDMAN S-91 MELANOMA IN THE CDBA-2F HYBRID MOUSE.
Topics: Animals; Benzaldehydes; beta-Cyclodextrins; Lasers; Lasers, Solid-State; Melanoma; Mice; Neoplasms; Neoplasms, Experimental; Photomicrography; Research | 1964 |