Novel polymer micelle mediated co-delivery of doxorubicin and P-glycoprotein siRNA for reversal of multidrug resistance and synergistic tumor therapy
| Autor: | Xiao-feng Zhou, Yang Liu, Chun Liu, Wei-liang Chen, Xue-nong Zhang, Chun-ge Zhang, Ji-zhao Li, Shu-di Yang, Wen-jing Zhu, Zhi-qiang Yuan |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
Cell Survival
Gene Expression Mice Nude ATP-binding cassette transporter 02 engineering and technology Pharmacology 010402 general chemistry 01 natural sciences Micelle Article Mice Drug Delivery Systems Downregulation and upregulation In vivo polycyclic compounds medicine Animals Humans Doxorubicin ATP Binding Cassette Transporter Subfamily B Member 1 RNA Small Interfering Micelles P-glycoprotein Antibiotics Antineoplastic Multidisciplinary biology Chemistry Liver Neoplasms technology industry and agriculture Hep G2 Cells Hydrogen-Ion Concentration 021001 nanoscience & nanotechnology Combined Modality Therapy Xenograft Model Antitumor Assays Drug Resistance Multiple In vitro Tumor Burden 0104 chemical sciences carbohydrates (lipids) Multiple drug resistance Drug Liberation Drug Resistance Neoplasm biology.protein Female 0210 nano-technology medicine.drug |
| Zdroj: | Scientific Reports |
| ISSN: | 2045-2322 |
| DOI: | 10.1038/srep23859 |
| Popis: | Co-delivery of chemotherapeutics and siRNA with different mechanisms in a single system is a promising strategy for effective cancer therapy with synergistic effects. In this study, a triblock copolymer micelle was prepared based on the polymer of N-succinyl chitosan–poly-L-lysine–palmitic acid (NSC–PLL–PA) to co-deliver doxorubicin (Dox) and siRNA–P-glycoprotein (P-gp) (Dox–siRNA-micelle). Dox–siRNA-micelle was unstable in pH 5.3 medium than in pH 7.4 medium, which corresponded with the in vitro rapid release of Dox and siRNA in acidic environments. The antitumor efficacy of Dox–siRNA-micelle in vitro significantly increased, especially in HepG2/ADM cells, which was due to the downregulation of P-gp. Moreover, almost all the Dox–siRNA-micelles accumulated in the tumor region beyond 24 h post-injection and the co-delivery system significantly inhibited tumor growth with synergistic effects in vivo. This study demonstrated the effectiveness of Dox–siRNA-micelles in tumor-targeting and MDR reversal and provided a promising strategy to develop a co-delivery system with synergistic effects for combined cancer therapy. |
| Databáze: | OpenAIRE |
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