Distinctive polymer micelle designed for siRNA delivery and reversal of MDR1 gene-dependent multidrug resistance

Autor: Shu-di Yang, Ben-gang You, Xue-nong Zhang, Ji-zhao Li, Chun-ge Zhang, Chun Liu, Zhi-qiang Yuan, Wen-jing Zhu, Wei-liang Chen, Xiao-feng Zhou, Yang Liu
Rok vydání: 2016
Předmět:
Zdroj: Journal of Biomedical Materials Research Part B: Applied Biomaterials. 105:2093-2106
ISSN: 1552-4973
DOI: 10.1002/jbm.b.33748
Popis: P-glycoprotein (P-gp) plays an importantrole in multidrug resistance (MDR), proved to be one of the major obstacles in cancer chemotherapy. Cationic polymers could specifically deliver siRNA to tumor cells and thus reverse MDR by the downregulation of P-gp. 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 deliver siRNA-P-gp (siRNA-micelle) or doxorubicin (Dox-micelle). The resulting micelle exhibited an efficient binding ability for siRNA and high encapsulation efficiency for Dox, with an average particle size of ∼170 nm. siRNA-micelle and Dox-micellewere instable at low pH, thereby enhancing tumor accumulation and intracellular release of the encapsulated siRNA and Dox. siRNA-micelle micelles could enhance the knockdown efficacy of siRNA by improving the transfection efficiency, downregulating P-gp expression, and passing the drug efflux transporters, thereby improving the therapeutic effects of Dox-micelle. However, P-gp could transfer from HepG2/ADM to HepG2 cells independent of the expression of mdr1, and the acquired resistance could permit tumor cells to survive and develop intrinsic P-gp-mediated resistance, thereby limiting the desired efficiency of chemotherapeutics. This study demonstrated the effectiveness of siRNA-micelle for tumor-targeted delivery, MDR reversal, and provided an effective strategy for the treatment of cancers that develop MDR. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 2093-2106, 2017.
Databáze: OpenAIRE
Externí odkaz: