gamma-cyclodextrin and Neoplasms

Different chemical agents are used for the biocompatibility and/or functionality of the nanoparticles used in magnetic hyperthermia to reduce or even eliminate cellular toxicity and to limit the interaction between them (van der Waals and magnetic dipolar interactions), with highly beneficial effects on the efficiency of magnetic hyperthermia in cancer therapy. In this paper we propose an innovative strategy for the biocompatibility of these nanoparticles using gamma-cyclodextrins (γ-CDs) to decorate the surface of magnetite (Fe

Topics: Biocompatible Materials; Cell Line, Tumor; Ferric Compounds; gamma-Cyclodextrins; Humans; Hyperthermia, Induced; Magnetics; Magnetite Nanoparticles; Metal Nanoparticles; Neoplasms; X-Ray Diffraction

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

We report here the tumor-implantable microparticles with a honeycomb-like porous structure. These microparticles were prepared by electrospinning using γ-cyclodextrin (γ-CD) conjugated with 3-(diethylamino)propylamine (DEAP, as a pH-responsive moiety), named γ-CD-DEAP. The resulting microparticles had pore channels (constructed using γ-CD-DEAP) extending into the deep compartment of the microparticles and allowing efficient paclitaxel (PTX, as a chemotherapeutic model drug) entrapment by a simple hole-filling encapsulation process. Importantly, the hydrophobic DEAP (at pH 7.4) in the γ-CD-DEAP microparticles changed to hydrophilic DEAP (at pH 6.8) because of its acidic pH-induced protonation. This phenomenon resulted in an acidic pH-activated particle destruction by a charge-charge repulsion between the protonated DEAP moieties and allowed a pH-triggered release of the encapsulated PTX from the collapsed microparticles. Consequently, γ-CD-DEAP microparticles implanted at the tumor site caused a significant enhancement of the in vitro/in vivo tumor cell ablation, suggesting their significant potential as a chemotherapeutic implant for tumor therapy.

Topics: Cell Line, Tumor; Doxorubicin; Drug Carriers; Drug Delivery Systems; Drug Liberation; gamma-Cyclodextrins; Humans; Hydrogen-Ion Concentration; Nanoparticles; Neoplasms; Paclitaxel; Polyethylene Glycols

The γ-cyclodextrin-based metal-organic framework (γ-CD-MOF) composite was designed and prepared toward targeted anticancer drug delivery and cancer therapy. Large amounts of graphene quantum dots (GQDs) were embedded in the γ-CD-MOF matrix (denoted as GQDs@γ-CD-MOF) to endow the γ-CD-MOF with strong fluorescence, which was then modified by pH responsive poly(ethyleneglycol)dimethacrylate (PEGMA) through surface initiated atom transfer radical polymerization (SI-ATRP) to fabricate the PEGMA@GQDs@γ-CD-MOF composite. Then, the cancer cell-targeted probe was obtained by immobilizing the AS1411 aptamer over it (denoted as AS1411@PEGMA@GQDs@γ-CD-MOF) and it exhibits pH-responsive release function and excellent targeting ability. Large amounts of antitumour drug, doxorubicin hydrochloride (DOX), could be encapsulated within this composite due to the chemical-rich functionality, and the resultant pH-responsive DOX delivery system (denoted as DOX/AS1411@PEGMA@GQDs@γ-CD-MOF) displayed a higher DOX loading of 89.1% with sustained release than the pristine γ-CD-MOF and GQDs@γ-CD-MOF. The targeting specificity investigation revealed that this DOX delivery system was effectively internalized via receptor mediated endocytosis with high selectivity. The in vivo antitumour study with tumour-bearing mice illustrated that the tumour growth can be effectively suppressed and partially ablated with negligible side effects after treatments. Therefore, the proposed AS1411@PEGMA@GQD@γ-CD-MOF composite is promising for effective DOX delivery and tumour growth inhibition both in vitro and in vivo, showing great potential for anticancer therapy.

Topics: Animals; Antineoplastic Agents; Aptamers, Nucleotide; Biocompatible Materials; Cell Line, Tumor; Cell Survival; Doxorubicin; Drug Carriers; Drug Liberation; gamma-Cyclodextrins; Graphite; Humans; Hydrogen-Ion Concentration; Metal-Organic Frameworks; Methacrylates; Mice; Mice, Nude; Neoplasms; Oligodeoxyribonucleotides; Polyethylene Glycols; Quantum Dots

Change in cellular pH due to onset of certain malfunctions needs to be tracked quickly so that treatment to cure such incidents may be started immediately. For example, microenvironment of a developing tumor is acidic due to high metabolic rate as well as low oxygen supply. Hence biomarkers that can sharply sense transition in pH could be of great use in the early detection of tumor formation. In the present work, a unique pH sensitive non-cytotoxic gold nanocluster based probe has been synthesized to precisely detect sharp change in biological pH. The gold nanoclusters were coated with dihydrolipoic acid incorporated γ-cyclodextrins. Measurements with steady state fluorometric changes reveal the sensibility of the probes through obvious wavelength shift depending on the changes in the microenvironment. The nanocluster based probe has been successfully applied to detect cancer cells with high precision.. Biomarkers sensitive to physiological environment have extensive uses in nanomedicines. pH sensitive ultrasmall gold nanoclusters coated with dihydrolipoic acid incorporated γ-cyclodextrins indicate Changes in cellular pH, therefore certain malfunctions. The new biomarker could be useful to detect tumor calls.

Topics: Biomarkers, Tumor; Cell Tracking; Cellular Microenvironment; Early Detection of Cancer; gamma-Cyclodextrins; Gold; Humans; Hydrogen-Ion Concentration; Metal Nanoparticles; Neoplasms; Thioctic Acid

For developing a multifunctional bioreducible targeted and synergistic co-delivery system for anticancer drug paclitaxel (PTX) and p53 gene for potential cancer therapy, supramolecular self-assembled inclusion complex was prepared from PTX and star-shaped cationic polymer containing γ-cyclodextrin (γ-CD) and multiple oligoethylenimine (OEI) arms with folic acid (FA) conjugated via a disulfide linker. The inclusion complex, termed as γ-CD-OEI-SS-FA/PTX, was formed between PTX and the hydrophobic cavity of γ-CD core of the star polymer. The γ-CD-OEI-SS-FA/PTX complex further formed polyplexes with pDNA to give positively charged nanoparticles, becoming multifunctional supramolecular self-assembled co-delivery system for PTX and pDNA targeting to cancer cells that overexpress folate receptors (FRs). The results showed that the FA-targeted function induced higher gene transfection efficiency in the FR-positive KB cells. The redox-sensitive disulfide linker in the self-assembly system led to the detachment of the FA groups from the carrier after the FR-mediated endocytosis, which resulted in the release of the bound FRs followed by the recycling of the FRs from the cytosol onto the cell membrane surface, facilitating continuous FR-mediated endocytosis to achieve enhanced gene transfection. In addition, the complexed PTX was co-delivered to the cells with pDNA, which further enhanced the gene transfection even at low N/P ratios in the FR-positive KB cells. Further, the efficient delivery of wild-type p53 gene resulted in large cell population at sub G1 and G2/M phases, inducing significant cell apoptosis. Therefore, the multifunctional γ-CD-OEI-SS-FA/PTX self-assembly system with the synergistic effects of redox-sensitive FA-targeted and PTX-enhanced p53 gene delivery may be promising for cancer therapeutic application.

Topics: Antineoplastic Agents, Phytogenic; Cell Line, Tumor; DNA; Drug Delivery Systems; Endocytosis; Folic Acid; gamma-Cyclodextrins; Genetic Therapy; Humans; Models, Molecular; Neoplasms; Paclitaxel; Transfection; Tumor Suppressor Protein p53

Small molecule inhibitors always exhibit poor water solubility due to the inherent hydrophobic property. It is an important challenge when they are developed as a real drug. S1, a structure-specific Bcl-2 inhibitor encountered this issue when moved forward in preclinical development. Herein, we prepared a 1:1 type of S1-gamma-cyclodextrin (S1-gamma-CD) inclusion complex to enhance the solubility. Bioevaluation of this new formulation was carried out totally in water solution. The cell internalization and cellular accumulation of S1-gamma-CD was illustrated by its fluorescence analogue S2. Disruption of Bcl-2/Bax heterodimerization in MCF-7 cells further revealed S1-gamma-CD could reach the subcellular function site. Moreover, the even stronger disruption by S1-gamma-CD than free S1 was found due to the higher local concentrations. Furthermore, the in vivo antitumor activity of S1-gamma-CD was evaluated in the H22 xenograft model. Results showed it exhibited significant antitumor activity with a decrease of tumor size (average tumor volume = 234 +/- 76 mm(3) vs control group, 398 +/- 121 mm(3), P < 0.01, and S1 group, 296 +/- 65 mm(3), P < 0.05), and a much longer survival time (the median time to the end point = 39.9 days vs control group, 29.2 days, P < 0.01). More importantly, the similar disruption of Bcl-2/Bax was found in S1-gamma-CD treated mice and free S1 treated ones. It demonstrated that S1-gamma-CD not only obtains a pharmaceutical level in vivo but also maintains the mechanism-based antitumor ability of S1 itself. It has been identified that cyclodextrin is appropriate to deliver a structure-specific molecule to its subcellular function site without any adverse effects on its mechanism-based potency, in either cultured cells or animals.

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; gamma-Cyclodextrins; Humans; Immunoprecipitation; Magnetic Resonance Spectroscopy; Mice; Mice, Inbred BALB C; Microscopy, Atomic Force; Microscopy, Confocal; Neoplasms; Proto-Oncogene Proteins c-bcl-2