Dataset Information

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

ABSTRACT: BACKGROUND This study aimed to prepare doxorubicin- and tetrahydrocurcumin-loaded and transferrin-modified PEG-PLGA nanoparticles (Tf-NPs-DOX-THC) for enhanced and synergistic chemoradiotherapy. MATERIAL AND METHODS Tf-NPs-DOX-THC were prepared via the double-emulsion method. The morphologies and particle sizes of the prepared nanoparticles were examined by TEM and DLS, respectively. The in vitro MTT, apoptosis, and clone formation assays were performed to detect the proliferation and radiosensitivity of cells with various treatments. Cellular uptake assay was also conducted. The tissue distribution of Tf-NPs was investigated by ex vivo DOX fluorescence imaging. The in vivo tumor growth inhibition efficiency of various treatments was evaluated in orthotopic C6 mouse models and C6 subcutaneously grafted mouse models. RESULTS Tf-NPs-DOX-THC exhibited high drug-loading efficiency (6.56±0.32%) and desirable particle size (under 250 nm). MTT, apoptosis, and clone formation assays revealed the enhanced anti-cancer activity and favorable radiosensitizing effect of Tf-NPs-DOX-THC. Strong fluorescence was observed in the brains of mice treated with Tf-NPs-DOX. The in vitro release of drug from nanoparticles was in a pH-sensitive manner. Tf-NPs-DOX-THC in combination with radiation also achieved favorable anti-tumor efficacy in vivo. CONCLUSIONS All results suggest that a combination of Tf-NPs-DOX-THC and radiation is a promising strategy for synergistic and sensitizing chemoradiotherapy of glioma.

SUBMITTER: Zhang X

PROVIDER: S-EPMC6934137 | biostudies-literature | 2019 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

Zhang Xingzhen X Zhao Lixia L Zhai Guangxi G Ji Jianbo J Liu Anchang A

Medical science monitor : international medical journal of experimental and clinical research 20191219

BACKGROUND This study aimed to prepare doxorubicin- and tetrahydrocurcumin-loaded and transferrin-modified PEG-PLGA nanoparticles (Tf-NPs-DOX-THC) for enhanced and synergistic chemoradiotherapy. MATERIAL AND METHODS Tf-NPs-DOX-THC were prepared via the double-emulsion method. The morphologies and particle sizes of the prepared nanoparticles were examined by TEM and DLS, respectively. The in vitro MTT, apoptosis, and clone formation assays were performed to detect the proliferation and radiosensi ...[more]

PMID: 31856143

Similar Datasets

Project description:The addition of polyethylene glycol (PEG) chains to poly(lactic-co-glycolic acid) (PLGA) matrices is extensively used to modulate the biodegradation, drug loading and release, mechanical properties, and chemical stability of the original system. Multiple parameters, including the molecular weight, relative concentration, polarity, and solubility, affect the physicochemical properties of the polymer blend. Here, molecular dynamics simulations with the united-atom 2016H66 force field are used to model the behavior of PLGA and PEG chains and thus predict the overall physicochemical features of the resulting blend. First, the model accuracy is validated against fundamental properties of pure PLGA and PEG samples. In agreement with previous experimental and theoretical observations, the PLGA solubility results to be higher in acetonitrile than in water, with Flory parameters νACN = 0.63 ± 0.01 and νW = 0.21 ± 0.02, and the Young's modulus of PLGA and PEG equal to Y = 2.0 ± 0.43 and 0.32 ± 0.34 GPa, respectively. Next, four PEG/PLGA blending regimes are identified by varying the relative concentrations and molecular weights of the individual polymers. The computational results demonstrate that at low PEG concentrations (<8% w/w), homogeneous blends are generated for both low and high PEG molecular weights. In contrast, at comparable PEG and PLGA concentrations (∼50% w/w), short PEG chains are only partially miscible whereas long PEG chains segregate within the PLGA matrix. This behavior has been confirmed experimentally via differential scanning calorimetry and is in agreement with previous observations. Finally, the computed Young's modulus of PLGA/PEG blends is observed to decrease with the PEG content returning the lowest values for the partial and fully segregated regimens (Y ≈ 1.3 GPa). This work proposes a computational scheme for predicting the physicochemical properties of PLGA/PEG blends paving the way toward the rational design of polymer mixtures for biomedical applications.

Project description:In a recent study, using an in vitro model to study intravaginal nanoparticle exposure during yeast infections, we demonstrated that C. albicans exposure suppressed apoptotic gene expression and induced oxidative stress and pyroptosis in vaginal epithelial cells. The mucous-penetrating drug delivery nanoparticles made from poly-(D, L-lactic-co-glycolic acid)-(polyethylene glycol) induced cytotoxicity by activating apoptosis, endoplasmic reticulum (ER) stress, oxidative stress, and DNA damage repair responses alone and, in some cases with C. albicans. In the current study we evaluated the effects of fluorescently-labelled nanoparticles in CBA/J mice challenged intravaginally for two hours followed by intravaginal challenge with C. albicans for 18 hours. Nanoparticle treatment increased systemic translocation of C. albicans threefold in the heart. C. albicans also increased systemic distribution of the nanoparticles fivefold in the heart. Flow cytometric assays showed co-localization of the nanoparticles with epithelial cells, macrophages and dendritic cells. Nanoparticle-treated, C. albicans-infected mice exhibited induction of autophagy, ER stress, apoptosis, and inflammatory serum cytokines. C. albicans infection was associated with pyroptosis and suppressed expression of ER stress and apoptosis-related genes. Induction of apoptosis during nanoparticle treatment and in nanoparticle-treated-C. albicans infected mice was observed as DNA damage responses, mitochondrial depolarization and (Poly [ADP-Ribose] Polymerase) cleavage. C. albicans infection was associated with increased mRNA expression of anti-apoptotic genes. Both C. albicans infection and nanoparticle treatment showed enhanced chemoattraction of dendritic cells and polymorphonuclear cells to factors in vaginal washings in a chemotaxis assay. This study shows that both intravaginal treatment of mice with the nanoparticles and infection with C. albicans induce cytotoxic and inflammatory responses. C. albicans also suppressed cell apoptosis. These results clarify our understanding of how nanoparticles modulate host cellular responses during C. albicans infection and will be applicable for future research and development of intravaginal nanomedicines.

Project description:Poly(lactic-co-glycolic acid) (PLGA) has been used in the field of tissue engineering as a scaffold due to its good biocompatibility, biodegradability and mechanical strength. With the aim to explore the degradability of PLGA electrospun nonwoven structures for oral mucosa tissue engineering applications, non-irradiated and gamma irradiated nonwovens were immersed in three different solutions, in which simulated body fluid (SBF) and artificial saliva are important for future oral mucosa tissue engineering. The nonwovens were immersed for 7, 15 and 30 days in SBF, culture media (DMEM) and artificial saliva at 37 °C. Before immersion in the solutions, the dosage of 15 kGy was applied for sterilization in one assay and compared with non-irradiated samples at the same timepoints. Samples were characterized using different techniques such as scanning electron microscopy (SEM), differential scanning calorimetric (DSC) and gel permeation chromatography (GPC) to evaluate the nonwoven degradation and Fourier-transform infrared spectroscopy (FTIR) to evaluate the chain scissions. Our results showed that PLGA nonwovens were constituted by semicrystalline fibers with moderate degradation properties up to thirty days. The non-irradiated samples exhibited slower kinetics of degradation than irradiated nonwovens. For immersion times longer than 7 days in the three different solutions, the mean diameter of irradiated fibers stayed in the same range, but significantly different from the control sample. On non-irradiated samples, the degradation kinetics was slower and the plateau in the diameter value was only attained after 30 days of immersion in the fluids. Plasticization (fluid absorption into the fiber structure) occurred in the bulk material, as confirmed by a decrease in Tg observed by DSC analyses of non-irradiated and irradiated nonwovens, in comparison with the respective controls. In addition, artificial saliva showed a higher capacity of influencing PLGA crystallization than SBF and DMEM. FTIR analyses showed typical PLGA chemical functional groups changes. These results will be important for future application of those PLGA electrospun nonwovens for oral mucosa regeneration.

Project description:Mucous-penetrating nanoparticles consisting of poly lactic acid-co-glycolic acid (PLGA)-polyethylene glycol (PEG) could improve targeting of microbicidal drugs for sexually transmitted diseases by intravaginal inoculation. Nanoparticles can induce inflammatory responses, which may exacerbate the inflammation that occurs in the vaginal tracts of women with yeast infections. This study evaluated the effects of these drug-delivery nanoparticles on VK2(E6/E7) vaginal epithelial cell proinflammatory responses to Candida albicans yeast infections. Vaginal epithelial cell monolayers were infected with C. albicans and exposed to 100 μg/ml 49.5 nm PLGA-PEG nanospheres or 20 μg/ml 1.1 x 500 nm PEG-functionalized graphene oxide (GO-PEG) sheets. The cells were assessed for changes in mRNA and protein expression of inflammation-related genes by RT-qPCR and physiological markers of cell stress using high content analysis and flow cytometry. C. albicans exposure suppressed apoptotic gene expression, but induced oxidative stress in the cells. The nanomaterials induced cytotoxicity and programmed cell death responses alone and with C. albicans. PLGA-PEG nanoparticles induced mRNA expression of apoptosis-related genes and induced poly (ADP-ribose) polymerase (PARP) cleavage, increased BAX/BCL2 ratios, and chromatin condensation indicative of apoptosis. They also induced autophagy, endoplasmic reticulum stress, and DNA damage. They caused the cells to excrete inflammatory recruitment molecules chemokine (C-X-C motif) ligand 1 (CXCL1), interleukin-1α (IL1A), interleukin-1β (IL1B), calprotectin (S100A8), and tumor necrosis factor α (TNF). GO-PEG nanoparticles induced expression of necrosis-related genes and cytotoxicity. They reduced autophagy and endoplasmic reticulum stress, and apoptotic gene expression responses. The results show that stealth nanoparticle drug-delivery vehicles may cause intracellular damage to vaginal epithelial cells by several mechanisms and that their use for intravaginal drug delivery may exacerbate inflammation in active yeast infections by increased inflammatory recruitment.

Dataset Information

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

Publications

Multifunctional Polyethylene Glycol (PEG)-Poly (Lactic-Co-Glycolic Acid) (PLGA)-Based Nanoparticles Loading Doxorubicin and Tetrahydrocurcumin for Combined Chemoradiotherapy of Glioma.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets