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Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In?Vitro and In?Vivo.

ABSTRACT: Mesoporous silica-based nanoparticles are generally accepted as a potential platform for drug loading with a lot of advantages, except for their complex purification procedures and structures that are difficult to decompose. In this work, biocompatible hyperbranched polyglycerol is introduced to synthesize mesoporous silica nanoparticles (MSNs). The materials possess good biocompatibility, controlled release, and biodegradability. They also show passive targeting capability through the enhanced permeability and retention effect and can be excreted from the biological system. The method avoids the needs to employ traditional surfactants and complicated purified procedures, which make these MSNs an efficient delivery system for cancer therapy.

SUBMITTER: Yang Y

PROVIDER: S-EPMC5288762 | biostudies-literature | 2017 Feb

REPOSITORIES: biostudies-literature

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Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In Vitro and In Vivo.

Yang Yang Y Wang Anhe A Wei Qiang Q Schlesener Cathleen C Haag Rainer R Li Qi Q Li Junbai J

ChemistryOpen 20161212 1

Mesoporous silica-based nanoparticles are generally accepted as a potential platform for drug loading with a lot of advantages, except for their complex purification procedures and structures that are difficult to decompose. In this work, biocompatible hyperbranched polyglycerol is introduced to synthesize mesoporous silica nanoparticles (MSNs). The materials possess good biocompatibility, controlled release, and biodegradability. They also show passive targeting capability through the enhanced ...[more]

PMID: 28168161

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Project description:BackgroundAs a promising nanocarrier in biomedical fields, silica nanoparticles (SiNPs) could transfer from the circulatory system to multiple organs. Among these, blood-liver molecular exchange is a critical factor in biological response to NPs. However, the potential effect of SiNPs on hepatic lipid metabolism is unclear. In this study, we employed three models to attempt discover whether and how SiNPs disturb hepatic lipid metabolism in vivo and in vitro.MethodsFirstly we used ICR mice models to evaulated the effects of SiNPs on the serum and hepatic lipid levels through repeated intravenous administration, meanwhile, the protein expressions of protein markers of lipogenesis (ACC1 and FAS), the key enzyme of fatty acid β-oxidation, CPT1A,and leptin levels in liver were detected by western blot. For verification studies, the model organism zebrafish and cultured hepatic L02 cells were further performed. The TLR5 and adipocytokine-signaling pathway were verified.ResultsInflammatory cell infiltration and mild steatosis induced by SiNPs were observed in the liver. Cholesterol, triglyceride, and low-density lipoprotein cholesterol levels were elevated significantly in both blood serum and liver tissue, whereas the ratio of high-density:low-density lipoprotein cholesterol was markedly decreased. Protein markers of lipogenesis (ACC1 and FAS) were elevated significantly in liver tissue, whereas the key enzyme of fatty acid β-oxidation, CPT1A, was decreased significantly. Interestingly, leptin levels in the SiNP-treated group were also elevated markedly. In addition, SiNPs caused hepatic damage and steatosis in zebrafish and enhanced hyperlipemia in high-cholesterol diet zebrafish. Similarly, SiNPs increased the release of inflammatory cytokines (IL1β, IL6, IL8, and TNFα) and activated the TLR5-signaling pathway in hepatic L02 cells.ConclusionIn summary, our study found that SiNPs triggered hyperlipemia and hepatic steatosis via the TLR5-signaling pathway. This suggests that regulation of TLR5 could be a novel therapeutic target to reduce side effects of NPs in living organisms.

Dataset Information

Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In?Vitro and In?Vivo.

Publications

Hyperbranched Polyglycerol-Induced Porous Silica Nanoparticles as Drug Carriers for Cancer Therapy In Vitro and In Vivo.

Similar Datasets

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