Low-density lipoprotein-coupled N-succinyl chitosan nanoparticles co-delivering siRNA and doxorubicin for hepatocyte-targeted therapy
| Autor: | Yi Zhou, Xue-nong Zhang, Shu-di Yang, Wei-liang Chen, Yang Liu, Qiao-Ling Zhu, Min Guan, Zhi-qiang Yuan, Aijun Zhu, Xiao-feng Zhou, Chun-ge Zhang, Chun Liu |
|---|---|
| Rok vydání: | 2014 |
| Předmět: |
Materials science
Cell Biophysics Mice Nude Bioengineering Flow cytometry law.invention Biomaterials Mice chemistry.chemical_compound Drug Delivery Systems Confocal microscopy law medicine Fluorescence microscope Animals Humans Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 RNA Small Interfering Chitosan Drug Carriers Antibiotics Antineoplastic medicine.diagnostic_test Cell growth Liver Neoplasms technology industry and agriculture Hep G2 Cells Molecular biology Drug Resistance Multiple Lipoproteins LDL medicine.anatomical_structure Liver chemistry Mechanics of Materials Low-density lipoprotein Hepatocyte Ceramics and Composites Nanoparticles Female lipids (amino acids peptides and proteins) medicine.drug |
| Zdroj: | Biomaterials. 35:5965-5976 |
| ISSN: | 0142-9612 |
| DOI: | 10.1016/j.biomaterials.2014.03.088 |
| Popis: | Developing safe and effective carriers of small interference RNA (siRNA) is a significant demand for the systemic delivery of siRNA. In this study, low-density lipoprotein (LDL) was isolated from human plasma and loaded with cholesterol-conjugated siRNA to silence the multidrug resistant gene of tumors. Chol-siRNA/LDL-coupled N-succinyl chitosan nanoparticles loaded with doxorubicin (Dox-siRNA/LDL-SCS-NPs) were then prepared and characterised. The Dox-siRNA/LDL-SCS-NPs had average particle size of 206.4 ± 9.2 nm, entrapment efficiency of 71.06% ± 1.42%, and drug-loading amount of 12.35% ± 0.87%. In vitro antitumor activity revealed that cell growth was significantly inhibited. The accumulation of Dox by fluorescence microscopy and flow cytometry showed that LDL-coupled nanoparticles were more easily taken up than Dox-SCS-NPs. Results of confocal microscopy and reverse transcription-PCR revealed the highly efficient uptake of siRNA and the decrease in mdr1 mRNA expression. LDL-coupled nanoparticles protected siRNA from macrophage phagocytosis by dynamic observation using live cell station. In vivo tumor-targeting suggested that Cy7-labelled Dox-LDL-SCS-NPs were markedly accumulated in an analyzed in situ liver tumor model. Results indicated that LDL-SCS-NPs were effective tumor-targeting vectors and that the preparation form may provide a new strategy for co-delivering siRNA and antitumor drugs. |
| Databáze: | OpenAIRE |
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