lactoferrin and Glioma

lactoferrin has been researched along with Glioma* in 20 studies

Reviews

1 review(s) available for lactoferrin and Glioma

ArticleYear
Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications.
    International journal of biological macromolecules, 2020, Dec-01, Volume: 164

    Lactoferrin (LF) is a naturally glycoprotein with iron-binding properties and diverse biological applications including; antiviral, anti-inflammatory, antioxidant, anti-cancer and immune stimulating effects. In addition, LF was found to be an ideal nanocarrier for some hydrophobic therapeutics because of its active targeting potential due to overexpression of its receptor on the surface of many cells. Moreover, it was proven to be a good candidate for fabrication of nanocarriers to specifically deliver drugs in case of brain tumors owing to the capability of LF to cross the blood brain barrier (BBB). Consequently, it seems to be a promising molecule with multiple applications in the field of cancer therapy and nanomedicine.

    Topics: Animals; Anti-Inflammatory Agents; Antineoplastic Agents; Antioxidants; Blood-Brain Barrier; Brain Neoplasms; Dietary Supplements; Drug Carriers; Drug Delivery Systems; Glioma; Humans; Lactoferrin; Mice; Micelles; Nanoparticles; Nanotechnology; Particle Size

2020

Other Studies

19 other study(ies) available for lactoferrin and Glioma

ArticleYear
Encapsulation of Au(III) Complex Using Lactoferrin Nanoparticles to Combat Glioma.
    Molecular pharmaceutics, 2023, 07-03, Volume: 20, Issue:7

    Metal-based drugs have been used for decades to treat solid cancers; however, these drugs have no significant therapeutic effect on glioma because they cannot effectively cross the blood-brain barrier (BBB). To develop a novel metal-based agent that can cross the BBB to target glioma, we synthesized an Au complex (C2) with remarkable glioma cytotoxicity and fabricated lactoferrin (LF)-C2 nanoparticles (LF-C2 NPs) as a novel therapy. We confirmed that C2 kills glioma cells by inducing apoptosis and autophagic death. The LF-C2 NPs cross the BBB, inhibit glioma growth, and selectively accumulate in the tumor tissue, significantly decreasing the side effects of C2. This study provides a novel strategy for applying metal-based agents to targeted therapy for glioma.

    Topics: Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Glioma; Humans; Lactoferrin; Nanoparticles

2023
Lactoferrin/phenylboronic acid-functionalized hyaluronic acid nanogels loading doxorubicin hydrochloride for targeting glioma.
    Carbohydrate polymers, 2021, Feb-01, Volume: 253

    Herein, lactoferrin (Lf)/phenylboronic acid (PBA)-functionalized hyaluronic acid nanogels crosslinked with disulfide-bond crosslinker was developed as a reduction-sensitive dual-targeting glioma therapeutic platform for doxorubicin hydrochloride (DOX) delivery (Lf-DOX/PBNG). Spherical Lf-DOX/PBNG with optimized physicochemical properties was obtained, and it could rapidly release the encapsulated DOX under high glutathione concentration. Moreover, enhanced cytotoxicity, superior cellular uptake efficiency, and significantly improved brain permeability of Lf-DOX/PBNG were observed in cytological studies compared with those of DOX solution, DOX-loaded PBA functionalized nanogels (DOX/PBNG), and Lf modified DOX-loaded nanogels (Lf-DOX/NG). The pharmacokinetic study exhibited that the area under the curve of DOX/PBNG, Lf-DOX/NG, and Lf-DOX/PBNG increased by 8.12, 4.20 and 4.32 times compared with that of DOX solution, respectively. The brain accumulation of Lf-DOX/PBNG was verified in biodistribution study to be 12.37 and 4.67 times of DOX solution and DOX/PBNG, respectively. These findings suggest that Lf-DOX/PBNG is an excellent candidate for achieving effective glioma targeting.

    Topics: Animals; Antibiotics, Antineoplastic; Boronic Acids; Brain; Brain Neoplasms; Cell Line, Tumor; Doxorubicin; Drug Carriers; Glioma; Hyaluronic Acid; Lactoferrin; Mice; Mice, Inbred ICR; Nanogels; Particle Size; Rats, Sprague-Dawley; Tissue Distribution

2021
Citric acid coated ultrasmall superparamagnetic iron oxide nanoparticles conjugated with lactoferrin for targeted negative MR imaging of glioma.
    Journal of biomaterials applications, 2021, Volume: 36, Issue:1

    The proposed study was to develop the preparation of ultrasmall superparamagnetic iron oxide nanoparticles (USPIONs) modified with citric acid, with surface conjugated with lactoferrin (Lf), which used as a potential targeted contrast agent for magnetic resonance imaging (MRI) of brain glioma. USPIONs were prepared by the thermal decomposition method. The hydrophobic USPIONs were coated with citric acid by the ligand exchange method. Then, Lf was conjugated into the surface of USPIONs. The obtained Lf-USPIONs were analyzed by fourier transform infrared (FTIR) spectroscopy and polyacrylamide gel electrophoresis. The size, size distribution, shape and superparamagnetic property of Lf-USPIONs were investigated with TEM and vibrating sample magnetometer (VSM). Both FTIR and electrophoresis analysis demonstrated the successful conjugation of Lf to the surface of USPIONs. The average size of Lf-USPIONs was about 8.4 ± 0.5 nm, which was determined using the statistics of measured over 100 nanoparticles in the TEM image, with a negative charge of -7.3 ± 0.2 mV. TEM imaging revealed that Lf-USPIONs were good in dispersion and polygonal in morphology. VSM results indicated that Lf-USPIONs were superparamagnetic and the saturated magnetic intensity was about 69.8 emu/g. The Lf-USPIONs also showed good biocompatibility in hemolysis, cytotoxicity, cell migration and blood biochemistry studies. MR imaging results in vitro and in vivo indicated that Lf-USPIONs exhibited good negative contrast enhancement. Taken together, Lf-USPIONs hold great potential for brain gliomas MR imaging as a nanosized targeted contrast agent.

    Topics: Animals; Cell Movement; Citric Acid; Contrast Media; Dextrans; Glioma; Hemolysis; Humans; Lactoferrin; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Nanoparticles; Rabbits; Rats

2021
Lactoferrin functionalized PEG-PLGA nanoparticles of shikonin for brain targeting therapy of glioma.
    International journal of biological macromolecules, 2018, Volume: 107, Issue:Pt A

    Shikonin (SHK) is a highly liposoluble naphthoquinone pigment has recently been investigated as a potential antiglioma agent. However, shikonin shows several limitations like poor aqueous solubility, short half-life and non-selective biodistribution. Herein, we have developed a nanoparticles (NPs) prepared from PEG-PLGA using an emulsion solvent evaporation method. Nanoparticle surfaces were modified by coating with lactoferrin (Lf) to improve the crossing of the blood brain barrier and targeting of glioma cells via receptor-mediated path-ways. X-ray powder diffraction and differential scanning calorimetry analysis revealed the amorphous nature of SHK encapsulated within the NPs. Moreover, the drug-loaded NPs exhibit narrow size distribution and high encapsulation efficiency. The in vitro release experiments of the NPs exhibited sustained release for more than 72h. When compared to free SHK and SHK/NPs, in vivo study demonstrated higher brain concentration of SHK, indicating a significant effect of Lf coated NPs on brain targeting. Accordingly, these findings provide evidence for the potential of Lf-modified NPs as a targeted delivery system for brain glioblastomas treatment.

    Topics: Animals; Brain; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Glioma; Humans; Lactoferrin; Nanoparticles; Naphthoquinones; Polyesters; Polyethylene Glycols; Rats; Tissue Distribution

2018
Nuclear and cytoplasmic delivery of lactoferrin in glioma using chitosan nanoparticles: Cellular location dependent-action of lactoferrin.
    European journal of pharmaceutics and biopharmaceutics : official journal of Arbeitsgemeinschaft fur Pharmazeutische Verfahrenstechnik e.V, 2018, Volume: 129

    Lactoferrin (Lf) exerts anti-cancer effects on glioma, however, the exact mechanism remains unclear. Despite possessing a nuclear localization sequence (NLS), Lf was found to allocate only in the cytoplasm of glioma 261. Lf was therefore loaded into nuclear and cytoplasmic targeted nanoparticles (NPs) to determine whether nuclear delivery of Lf would enhance its anti-cancer effect. Upon treatment with 300 and 800 µg/mL Lf loaded chitosan NPs, nuclear targeted Lf-NPs showed 1.3 and 2.7 folds increase in cell viability, whereas cytoplasmic targeted Lf-NPs at 300 µg/mL decreased cell viability by 0.8 folds in comparison to free Lf and controls. Results suggest that the cytotoxicity of Lf on glioma is attributable to its cytoplasmic allocation. Nuclear delivery of Lf induced cell proliferation rather than cytotoxicity, indicating that the mode of action of Lf in glioma is cell location dependent. This calls for caution about the general use of Lf as an anti-cancer protein.

    Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Nucleus; Cell Proliferation; Cell Survival; Chitosan; Cytoplasm; Drug Carriers; Glioma; Lactoferrin; Mice; Nanoparticles; Permeability

2018
Antiglioma via regulating oxidative stress and remodeling tumor-associated macrophage using lactoferrin-mediated biomimetic codelivery of simvastatin/fenretinide.
    Journal of controlled release : official journal of the Controlled Release Society, 2018, 10-10, Volume: 287

    Effective treatment of malignant glioma still remains a formidable challenge due to lack of the effective BBB-permeable drugs and efficient brain delivery methods, and the pharmacotherapy options are very limited. Therefore, to develop an effective therapeutic strategy is a pressing need. In this work, a noncytotoxic drug combination (i.e., simvastatin and fenretinide) was revealed to be potent for treating glioma, which was co-encapsulated into a TPGS-TAT-embedded lactoferrin nanoparticle system for achieving brain-targeted biomimetic delivery via the LRP-1 receptor. It was shown that the lactoferrin nanoparticle repolarized the tumor-associated macrophages from the M2 phenotype to M1 via regulating the STAT6 pathway, as well as induced the ROS-mediated mitochondrial apoptosis by inhibiting the Ras/Raf/p-Erk pathway in the glioma cells. The antiglioma efficacy was further demonstrated in both the subcutaneous and orthotopic glioma models. The repolarization of tumor-associated macrophages not only prompted the ROS generation but also induced the innate immunity (e.g., antitumor cytokine release). This delivery and therapeutic strategy provides a novel modality for the glioma treatment.

    Topics: Animals; Brain Neoplasms; Cell Line, Tumor; Drug Carriers; Drug Delivery Systems; Female; Fenretinide; Glioma; Humans; Lactoferrin; Macrophages; Male; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Nude; Nanoparticles; Oxidative Stress; Simvastatin

2018
Antitumor efficacy of Lf modified daunorubicin plus honokiol liposomes in treatment of brain glioma.
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2017, Aug-30, Volume: 106

    Malignant brain glioma is the most common and aggressive type of primary intracranial neoplasm. Regular chemotherapy cannot eradicate brain glioma cells and the residual glioma cells could form vasculogenic mimicry (VM) channels under hypoxic conditions to provide nutrients for tumor cell invasion. In addition, the existence of the blood-brain barrier (BBB) restricts most antitumor drugs into brain glioma. In this study, we developed a kind of lactoferrin (Lf) modified daunorubicin plus honokiol liposomes to transport antitumor drugs across BBB, eliminate the VM channels and block tumor cell invasion. The evaluations were performed on BBB model, brain glioma cells and glioma-bearing mice. In vitro results showed that the targeting liposomes with suitable physicochemical property could enhance the drug transportation acrossing the BBB, inhibit C6 cells invasion and destroy VM channels. Action mechanism studies indicated that Lf modified daunorubicin plus honokiol liposomes could activate apoptotic enzymes caspase 3 as well as down-regulate VM protein indicators (PI3K, MMP-2, MMP-9, VE-Cadherin and FAK). In vivo results displayed the targeting liposomes improved accumulation in brain tumor tissue and exhibited obvious antitumor efficacy. Therefore, Lf modified daunorubicin plus honokiol liposomes could be used as a potential therapy for treatment of brain glioma.

    Topics: Animals; Antibiotics, Antineoplastic; Apoptosis; Biphenyl Compounds; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Daunorubicin; Drug Liberation; Glioma; Lactoferrin; Lignans; Liposomes; Mice, Inbred ICR; Rats

2017
Overcoming blood brain barrier with a dual purpose Temozolomide loaded Lactoferrin nanoparticles for combating glioma (SERP-17-12433).
    Scientific reports, 2017, 07-26, Volume: 7, Issue:1

    Targeted delivery of drugs to the brain is challenging due to the restricted permeability across the blood brain barrier (BBB). Gliomas are devastating cancers and their positive treatment outcome using Temozolomide (TMZ) is limited due to its short plasma half-life, systemic toxicity and limited access through the blood-brain barrier (BBB). Nanoparticles made of Lactoferrin (Lf) protein, have been shown to enhance the pharmacological properties of drugs. Here, we report the specific ability of Lf nanoparticles to cross BBB and target over-expressed Lf receptors on glioma for enhanced TMZ delivery. TMZ-loaded Lf nanoparticles (TMZ-LfNPs) were prepared by our previously reported sol-oil method. While the Lf protein in the NP matrix aids in transcytosis across the BBB and preferential tumor cell uptake, the pH responsiveness leads to TMZ release exclusively in the tumor microenvironment. Delivery through LfNPs results in an enhanced and sustained intracellular concentration of TMZ in GL261 cells in vitro along with improving its in vivo pharmacokinetics and brain accumulation. TMZ-LfNPs treatment results in a significant reduction of tumor volume, higher tumor cell apoptosis and improved median survival in glioma bearing mice. These results demonstrate that LfNPs present an efficient TMZ delivery platform for an effective treatment of gliomas.

    Topics: Animals; Antineoplastic Agents, Alkylating; Blood-Brain Barrier; Cell Line, Tumor; Drug Carriers; Glioma; Lactoferrin; Mice; Nanoparticles; Temozolomide; Treatment Outcome

2017
Glioma Dual-Targeting Nanohybrid Protein Toxin Constructed by Intein-Mediated Site-Specific Ligation for Multistage Booster Delivery.
    Theranostics, 2017, Volume: 7, Issue:14

    Malignant glioma is one of the most untreatable cancers because of the formidable blood-brain barrier (BBB), through which few therapeutics can penetrate and reach the tumors. Biologics have been booming in cancer therapy in the past two decades, but their application in brain tumor has long been ignored due to the impermeable nature of BBB against effective delivery of biologics. Indeed, it is a long unsolved problem for brain delivery of macromolecular drugs, which becomes the Holy Grail in medical and pharmaceutical sciences. Even assisting by targeting ligands, protein brain delivery still remains challenging because of the synthesis difficulties of ligand-modified proteins. Herein, we propose a rocket-like, multistage booster delivery system of a protein toxin, trichosanthin (TCS), for antiglioma treatment. TCS is a ribosome-inactivating protein with the potent activity against various solid tumors but lack of specific action and cell penetration ability. To overcome the challenge of its poor druggability and site-specific modification, intein-mediated ligation was applied, by which a gelatinase-cleavable peptide and cell-penetrating peptide (CPP)-fused recombinant TCS toxin can be site-specifically conjugated to lactoferrin (LF), thus constructing a BBB-penetrating, gelatinase-activatable cell-penetrating nanohybrid TCS toxin. This nanohybrid TCS system is featured by the multistage booster strategy for glioma dual-targeting delivery. First, LF can target to the BBB-overexpressing low-density lipoprotein receptor-related protein-1 (LRP-1), and assist with BBB penetration. Second, once reaching the tumor site, the gelatinase-cleavable peptide acts as a separator responsive to the glioma-associated matrix metalloproteinases (MMPs), thus releasing to the CPP-fused toxin. Third, CPP mediates intratumoral and intracellular penetration of TCS toxin, thereby enhancing its antitumor activity. The BBB penetration and MMP-2-activability of this delivery system were demonstrated. The antiglioma activity was evaluated in the subcutaneous and orthotopic animal models. Our work provides a useful protocol for improving the druggability of such class of protein toxins and promoting their

    Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Cell-Penetrating Peptides; Glioma; HeLa Cells; Humans; Inteins; Lactoferrin; Low Density Lipoprotein Receptor-Related Protein-1; Male; Matrix Metalloproteinase 2; MCF-7 Cells; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Protein Binding; Trichosanthin

2017
Dual-Targeting Lactoferrin-Conjugated Polymerized Magnetic Polydiacetylene-Assembled Nanocarriers with Self-Responsive Fluorescence/Magnetic Resonance Imaging for In Vivo Brain Tumor Therapy.
    Advanced healthcare materials, 2016, Volume: 5, Issue:6

    Maintaining a high concentration of therapeutic agents in the brain is difficult due to the restrictions of the blood-brain barrier (BBB) and rapid removal from blood circulation. To enable controlled drug release and enhance the blood-brain barrier (BBB)-crossing efficiency for brain tumor therapy, a new dual-targeting magnetic polydiacetylene nanocarriers (PDNCs) delivery system modified with lactoferrin (Lf) is developed. The PDNCs are synthesized using the ultraviolet (UV) cross-linkable 10,12-pentacosadiynoic acid (PCDA) monomers through spontaneous assembling onto the surface of superparamagnetic iron oxide (SPIO) nanoparticles to form micelles-polymerized structures. The results demonstrate that PDNCs will reduce the drug leakage and further control the drug release, and display self-responsive fluorescence upon intracellular uptake for cell trafficking and imaging-guided tumor treatment. The magnetic Lf-modified PDNCs with magnetic resonance imaging (MRI) and dual-targeting ability can enhance the transportation of the PDNCs across the BBB for tracking and targeting gliomas. An enhanced therapeutic efficiency can be obtained using Lf-Cur (Curcumin)-PDNCs by improving the retention time of the encapsulated Cur and producing fourfold higher Cur amounts in the brain compared to free Cur. Animal studies also confirm that Lf targeting and controlled release act synergistically to significantly suppress tumors in orthotopic brain-bearing rats.

    Topics: Animals; Antineoplastic Agents; Blood-Brain Barrier; Brain Neoplasms; Cell Line, Tumor; Cell Survival; Curcumin; Drug Carriers; Ferric Compounds; Glioma; Lactoferrin; Magnetic Resonance Imaging; Magnetite Nanoparticles; Male; Particle Size; Polyacetylene Polymer; Polymers; Polyynes; Rats; Rats, Inbred F344; Survival Rate; Ultraviolet Rays

2016
A pH-sensitive hyaluronic acid prodrug modified with lactoferrin for glioma dual-targeted treatment.
    Materials science & engineering. C, Materials for biological applications, 2016, Oct-01, Volume: 67

    Gliomas are the most common and lethal type of primary malignant brain tumor. But the existence of blood brain barrier (BBB) and blood-tumor barrier (BTB) hinder drug from reaching the tumor site. To address this problem, we developed a novel prodrug (Lf-HA-DOX) by conjugating hyaluronic acid with doxorubicin (HA-DOX) by an acid-labile hydrazone linkage, which is released in an acidic environment and accumulates in tumor tissues. Lactoferrin (Lf) was coupled for transporting across the BBB. In vitro, the release of DOX from Lf-HA-DOX was pH-dependent. At lower pH (5.0 and 6.0), the release of DOX was much quicker than that at pH7.4. In the cellular uptake studies, flow cytometry analyses and confocal laser scanning microscopy results showed significantly enhanced cellular uptake of Lf-HA-DOX and HA-DOX in C6 cells compared to DOX. In BALB/C mice bearing C6 glioma, enhanced accumulation of Lf-HA-DOX in the glioma was observed by real time fluorescence image. Correspondingly, glioma-bearing mice treated with Lf-HA-DOX displayed the longest median survival time, which was 2-fold longer than that of saline group. In conclusion, Lf-HA-DOX was able to significantly increase drug delivery to the glioma, which might provide a promising strategy for antiglioma therapy.

    Topics: Animals; Cell Line, Tumor; Delayed-Action Preparations; Doxorubicin; Glioma; Humans; Hyaluronic Acid; Hydrogen-Ion Concentration; Lactoferrin; Mice; Mice, Nude; Prodrugs; Rats; Xenograft Model Antitumor Assays

2016
Novel lactoferrin-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) copolymer nanobubbles for tumor-targeting ultrasonic imaging.
    International journal of nanomedicine, 2015, Volume: 10

    In the study reported here, a novel amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) (PAEEP-PLLA) copolymer was synthesized by ring-opening polymerization reaction. The perfluoropentane-filled PAEEP-PLLA nanobubbles (NBs) were prepared using the O1/O2/W double-emulsion and solvent-evaporation method, with the copolymer as the shell and liquid perfluoropentane as the core of NBs. The prepared NBs were further conjugated with lactoferrin (Lf) for tumor-cell targeting. The resulting Lf-conjugated amphiphilic poly(aminoethyl ethylene phosphate)/poly(L-lactide) nanobubbles (Lf-PAEEP-PLLA NBs) were characterized by photon correlation spectroscopy, polyacrylamide gel electrophoresis, Fourier transform infrared spectroscopy, and transmission electron microscopy. The average size of the Lf-PAEEP-PLLA NBs was 328.4±5.1 nm, with polydispersity index of 0.167±0.020, and zeta potential of -12.6±0.3 mV. Transmission electron microscopy imaging showed that the Lf-PAEEP-PLLA NBs had a near-spherical structure, were quite monodisperse, and there was a clear interface between the copolymer shell and the liquid core inside the NBs. The Lf-PAEEP-PLLA NBs also exhibited good biocompatibility in cytotoxicity and hemolysis studies and good stability during storage. The high cellular uptake of Lf-PAEEP-PLLA NBs in C6 cells (low-density lipoprotein receptor-related protein 1-positive cells) at concentrations of 0-20 µg/mL indicated that the Lf provided effective targeting for brain-tumor cells. The in vitro acoustic behavior of Lf-PAEEP-PLLA NBs was evaluated using a B-mode clinical ultrasound imaging system. In vivo ultrasound imaging was performed on tumor-bearing BALB/c nude mice, and compared with SonoVue(®) microbubbles, a commercial ultrasonic contrast agent. Both in vitro and in vivo ultrasound imaging indicated that the Lf-PAEEP-PLLA NBs possessed strong, long-lasting, and tumor-enhanced ultrasonic contrast ability. Taken together, these results indicate that Lf-PAEEP-PLLA NBs represent a promising nano-sized ultrasonic contrast agent for tumor-targeting ultrasonic imaging.

    Topics: Animals; Cell Proliferation; Diagnostic Imaging; Ethylenes; Glioma; Hemolysis; Human Umbilical Vein Endothelial Cells; Lactoferrin; Mice; Mice, Inbred BALB C; Mice, Nude; Micelles; Microbubbles; Phosphates; Polyesters; Polymers; Rats, Sprague-Dawley; Tumor Cells, Cultured; Ultrasonics

2015
Lactoferrin conjugated iron oxide nanoparticles for targeting brain glioma cells in magnetic particle imaging.
    Nanoscale, 2015, Oct-28, Volume: 7, Issue:40

    Magnetic Particle Imaging (MPI) is a new real-time imaging modality, which promises high tracer mass sensitivity and spatial resolution directly generated from iron oxide nanoparticles. In this study, monodisperse iron oxide nanoparticles with median core diameters ranging from 14 to 26 nm were synthesized and their surface was conjugated with lactoferrin to convert them into brain glioma targeting agents. The conjugation was confirmed with the increase of the hydrodynamic diameters, change of zeta potential, and Bradford assay. Magnetic particle spectrometry (MPS), performed to evaluate the MPI performance of these nanoparticles, showed no change in signal after lactoferrin conjugation to nanoparticles for all core diameters, suggesting that the MPI signal is dominated by Néel relaxation and thus independent of hydrodynamic size difference or presence of coating molecules before and after conjugations. For this range of core sizes (14-26 nm), both MPS signal intensity and spatial resolution improved with increasing core diameter of nanoparticles. The lactoferrin conjugated iron oxide nanoparticles (Lf-IONPs) showed specific cellular internalization into C6 cells with a 5-fold increase in MPS signal compared to IONPs without lactoferrin, both after 24 h incubation. These results suggest that Lf-IONPs can be used as tracers for targeted brain glioma imaging using MPI.

    Topics: Brain Neoplasms; Cell Line, Tumor; Drug Delivery Systems; Ferric Compounds; Glioma; Humans; Immobilized Proteins; Lactoferrin; Magnetite Nanoparticles; Molecular Imaging

2015
Co-administration of dual-targeting nanoparticles with penetration enhancement peptide for antiglioblastoma therapy.
    Molecular pharmaceutics, 2014, Jan-06, Volume: 11, Issue:1

    Chemotherapy is an indispensable auxiliary treatment for glioma but highly limited by the existence of both blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). The dysfunctional brain tumor blood vessels and high interstitial pressure in glioma also greatly hindered the accumulation and deep penetration of chemotherapeutics into the glioma. Lactoferrin (Lf), with its receptor overexpressed on both the brain endothelial cells and glioma cells, was here functionalized to the surface of poly(ethylene glycol)-poly(lactic acid) nanoparticles to mediate BBB/BBTB and glioma cell dual targeting. tLyP-1, a tumor-homing peptide, which contains a C-end Rule sequence that can mediate tissue penetration through the neuropilin-1-dependent internalization pathway, was coadministrated with Lf-functionalized nanoparticles (Lf-NP) to enhance its accumulation and deep penetration into the glioma parenchyma. Enhanced cellular association in both BCEC and C6 cells, increased cytotoxicity of the loaded paclitaxel, and deep penetration in the 3D glioma spheroids was achieved by Lf-NP. Following coadministration with tLyP-1, the functionalized nanoparticles obtained improved tumor targeting, glioma vascular extravasation, and antiglioma efficacy. The findings here suggested that the strategy by coadministrating BBB/BBTB and glioma cells dual-targeting nanocarriers with a tumor penetration enhancement peptide represent a promising platform for antiglioma drug delivery.

    Topics: Animals; Antineoplastic Agents, Phytogenic; Blood-Brain Barrier; Brain; Cells, Cultured; Drug Delivery Systems; Endothelium, Vascular; Glioma; Lactates; Lactoferrin; Male; Mice; Mice, Inbred BALB C; Mice, Nude; Nanoparticles; Paclitaxel; Peptides, Cyclic; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Spheroids, Cellular; Tissue Distribution

2014
Lactoferrin-modified poly(ethylene glycol)-grafted BSA nanoparticles as a dual-targeting carrier for treating brain gliomas.
    Molecular pharmaceutics, 2014, Jun-02, Volume: 11, Issue:6

    In this study, a dual-targeting drug delivery system based on bovine serum albumin nanoparticles (BSA-NPs) modified with both lactoferrin (Lf) and mPEG2000 loading doxorubicin (DOX) was designed, and its blood-brain barrier (BBB) penetration and brain glioma cells targeting properties were explored. BSA-NPs were prepared by a desolvation technique, and mPEG2000 was incorporated onto the surface of BSA-NPs by reacting with the free amino-group of BSA to form mPEG2000-modified BSA-NPs (P2000-NPs). Finally, Lf-modified P2000-NPs (Lf-NPs) was obtained by absorbing Lf onto the surface of P2000-NPs via the positive and negative charges interaction at physiological pH. Three levels of mPEG2000 and Lf-modified NPs were prepared and characterized, respectively. The uptake and potential cytotoxicity of different DOX preparations in vitro by the primary brain capillary endothelial cells (BCECs) and glioma cells (C6) were investigated. The dual-targeting effects were studied on the BBB model in vitro, BCECs/C6 glioma coculture model in vitro, and C6 glioma-bearing rats in vivo, respectively. The results exhibited that, with the increase of the amount of both mPEG2000 and Lf, the particle size of NPs increased and its zeta potential decreased. The in vivo pharmacokinetics study in healthy rats exhibited that P2000-NPs with a high level of mPEG2000 (P2000H-NPs) had longer circulation time in vivo. Compared to other NPs, Lf-NPs with high level of both Lf and mPEG2000 (LfH-NPs) showed the strongest cytotoxicity and the highest effectiveness in the uptake both in BCECs and C6 as well as improved the dual-targeting effects. Body distribution of DOX in different formulations revealed that LfH-NPs could significantly increase the accumulation of DOX in the brain, especially at 2 h postinjection (P < 0.05). In conclusion, Lf-NPs were a prospective dual-targeting drug delivery system for effective targeting therapy of brain gliomas.

    Topics: Animals; Antibiotics, Antineoplastic; Blood-Brain Barrier; Brain Neoplasms; Chemistry, Pharmaceutical; Doxorubicin; Drug Carriers; Drug Delivery Systems; Endothelial Cells; Glioma; Lactoferrin; Nanoparticles; Particle Size; Polyethylene Glycols; Rats; Rats, Sprague-Dawley; Serum Albumin, Bovine; Tissue Distribution

2014
pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin for MR and fluorescence imaging of glioma in rats.
    Biomaterials, 2013, Volume: 34, Issue:30

    Glioma is the most common primary brain tumor and causes a disproportionate level of morbidity and mortality across a wide range of individuals. From previous clinical practices, definition of glioma margin is the key point for surgical resection. In order to outline the exact margin of glioma and provide a guide effect for the physicians both at pre-surgical planning stage and surgical resection stage, pH/temperature sensitive magnetic nanogels conjugated with Cy5.5-labled lactoferrin (Cy5.5-Lf-MPNA nanogels) were developed as a promising contrast agent. Due to its pH/te mperature sensitivity, Cy5.5-Lf-MPNA nanogels could change in its hydrophilic/hydrophobic properties and size at different pH and temperatures. Under physiological conditions (pH 7.4, 37 °C), Cy5.5-Lf-MPNA nanogels were hydrophilic and swollen, which could prolong the blood circulation time. In the acidic environment of tumor tissues (pH 6.8, 37 °C), Cy5.5-Lf-MPNA nanogels became hydrophobic and shrunken, which could be more easily accumulated in tumor tissue and internalized by tumor cells. In addition, lactoferrin, an effective targeting ligand for glioma, provides active tumor targeting ability. In vivo studies on rats bearing in situ glioma indicated that the MR/fluorescence imaging with high sensitivity and specificity could be acquired using Cy5.5-Lf-MPNA nanogels due to active targeting function of the Lf and enhancement of cellular uptake by tailoring the hydrophilic/hydrophobic properties of the nanogels. With good biocompatibility shown by cytotoxicity assay and histopathological analysis, Cy5.5-Lf-MPNA nanogels are hopeful to be developed as a specific and high-sensitive contrast agent for preoperative MRI and intraoperative fluorescence imaging of glioma.

    Topics: Acrylic Resins; Animals; Biocompatible Materials; Brain Neoplasms; Carbocyanines; Cell Line, Tumor; Fluorescence; Glioma; History, 20th Century; Hydrogen-Ion Concentration; Lactoferrin; Magnetic Phenomena; Magnetic Resonance Imaging; Male; Materials Testing; Mice; Nanogels; NIH 3T3 Cells; Particle Size; Polyethylene Glycols; Polyethyleneimine; Rats; Rats, Wistar; Staining and Labeling; Temperature

2013
Lactoferrin-conjugated superparamagnetic iron oxide nanoparticles as a specific MRI contrast agent for detection of brain glioma in vivo.
    Biomaterials, 2011, Volume: 32, Issue:2

    A specific contrast agent for magnetic resonance imaging (MRI) is crucial to brain tumor patients for the surgical operation or the postoperative radiology. This study explored lactoferrin-conjugated superparamagnetic iron oxide nanoparticles (Lf-SPIONs) as an MRI contrast agent for the detection of brain gliomas in vivo. The hydrodynamic diameter of about 75 nm, saturation magnetization of 51 emu/g Fe and T(2) relaxivity of 75.6 mM(-1)S(-1) of the Lf-SPIONs suggested its applicability for MRI. Using a rat model of C6 glioma, Lf-SPIONs provided a better picture or more sensitivity to depict brain glioma on MR images than that of SPIONs. Significantly enhanced T(2)-weighted images of brain glioma were documented in vivo with Lf-SPIONs until 48 h after injection. Moreover, Lf-SPIONs were clearly observed around vascular region of the tumor slices after 48 h. High level expression of Lf receptors was confirmed in brain tumor tissues by RT-PCR and Western Blot compared to normal brain tissues. These findings suggested that Lf-SPIONs could be potentially employed as a sensitive and specific MRI contrast agent in the diagnosis of brain glioma.

    Topics: Animals; Blotting, Western; Cell Line; Cell Line, Tumor; Contrast Media; Ferrosoferric Oxide; Glioma; Humans; Lactoferrin; Magnetic Resonance Imaging; Nanoparticles; Rats; Reverse Transcriptase Polymerase Chain Reaction

2011
Lactoferrin modified doxorubicin-loaded procationic liposomes for the treatment of gliomas.
    European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences, 2011, Sep-18, Volume: 44, Issue:1-2

    In this study, a brain-targeted chemotherapeutical delivery system, doxorubicin-loaded lactoferrin-modified procationic liposome (DOX-Lf-PCL) was developed, and its therapeutic effect for glioma was evaluated. The uptake profile of various DOX formulations in vitro by primary brain capillary endothelial cells (BCECs) and glioma cell C6 were studied by laser scanning confocal microscope and flow cytometry. An intracranial tumor model of rats was employed to evaluate the therapeutic effect of DOX-Lf-PCLs for glioma. Five groups of glioma-bearing rats (total n=50) were subjected to three cycles of 2.5mg/kg body weight of doxorubicin in different formulations or normal saline (N.S.) and analyzed for survival (median survival time, Kaplan-Meier). The results indicated that compared with the DOX solution or DOX-loaded conventional liposomes (DOX-Lips), DOX-PCLs and DOX-Lf-PCLs showed an improved performance in the uptake efficiency in BCECs and C6 cells. The DOX-Lf-PCLs can inhibit the growth of C6 more efficiently in vitro than other DOX formulations. The endocytosis involved in the DOX-Lf-PCLs uptake of C6 was mediated by both receptor- and absorption-mediated transcytosis. DOX-Lf-PCLs could significantly extend the survival time compared with the N.S. control and other DOX formulations. This study showed that the therapy with DOX-Lf-PCLs offers an effective therapeutic potential for gliomas.

    Topics: Animals; Antibiotics, Antineoplastic; Brain Neoplasms; Cations; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Drug Carriers; Drug Compounding; Endothelial Cells; Glioma; Kaplan-Meier Estimate; Lactoferrin; Liposomes; Male; Mice; Microscopy, Confocal; Particle Size; Rats; Rats, Wistar; Surface Properties; Tissue Distribution; Xenograft Model Antitumor Assays

2011
Lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine for chemotherapy of glioma rats.
    Molecular pharmaceutics, 2010, Dec-06, Volume: 7, Issue:6

    The blood-brain barrier (BBB) and multidrug resistance (MDR) are the main causes for poor prognosis of glioma patients after chemotherapy. To explore the way for settling this problem, in this study, a novel antitumor agent loaded drug delivery system, lactoferrin-conjugated biodegradable polymersome holding doxorubicin and tetrandrine (Lf-PO-Dox/Tet), integrating both BBB and glioma-targeting moiety and MDR inhibitor, was designed and its chemotherapy for glioma rats was evaluated. Biodegradable polymersome (PO) encapsulating both doxorubicin (Dox) and tetrandrine (Tet) was prepared by the thin-film hydration method (PO-Dox/Tet) and then conjugated with lactoferrin (Lf) to yield Lf-PO-Dox/Tet with an average diameter around 220 nm and surface Lf molecule number per polymersome around 40. Compared with PO-DOX, PO-Dox/Tet, and Lf-PO-Dox, Lf-PO-Dox/Tet demonstrated the strongest cytotoxicity against C6 glioma cells and the greatest uptake index by C6 cells. In vivo imaging analysis indicated that Lf-PO labeled with a near-infrared dye could enter the brain and accumulate at the tumor site. Pharmacokinetics and tissue distribution results also showed that Lf-PO-Dox/Tet accumulated more in the right hemisphere than other groups of polymersomes. Pharmacodynamics results revealed that tumor volume of the Lf-PO-Dox/Tet group was significantly smaller than that of other therapeutic groups, and the median survival time of Lf-PO-Dox/Tet group was longer than that of Lf-PO-Dox group and significantly longer than those of the other three therapeutic groups. These results suggested that Lf-PO-Dox/Tet could have therapeutic potential for gliomas.

    Topics: Animals; Antineoplastic Combined Chemotherapy Protocols; Benzylisoquinolines; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Delivery Systems; Glioma; Lactoferrin; Particle Size; Polymers; Rats; Rats, Sprague-Dawley; Surface Properties; Tissue Distribution; Xenograft Model Antitumor Assays

2010