Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
10229490 | Biomaterials | 2012 | 12 Pages |
Abstract
A star-shape copolymer of nanostructure-forming material, P-glycoprotein (P-gp) reversible inhibitor and anticancer enhancer, lysine-linked di-tocopherol polyethylene glycol 2000 succinate (PLV2K), was synthesized to overcome multidrug resistance (MDR) in cancer chemotherapy. The critical micellar concentration of PLV2K was as low as 1.14 μg/mL, which can endow nanoassemblies good physical stability. Doxorubicin (DOX) was encapsulated into the hydrophobic core of PLV2K (PLV2K-DOX), with encapsulation efficiency as high as 94.5% and a particle size of 16.4 nm. DOX released from PLV2K-DOX nanomicelles was pH-dependent, which ensures micelles stable in blood circulation and releases DOX within tumor cells. Facilitated by the cytotoxicity and uncompetitive P-gp ATPase inhibition by PLV2K, PLV2K-DOX showed greater cytotoxicity compared with DOX solution with increased intracellular accumulation in resistant MCF-7/Adr cells. PLV2K-DOX nanomicelles were uptaken into MCF-7/Adr cells via macropinocytosis and caveolae-mediated endocytosis, which further facilitate escapement of P-gp efflux. The anticancer efficacy in vivo was evaluated in 4T1-bearing mice and inhibition of tumor by PLV2K-DOX was more effective than TPGS-DOX and DOX solution. In summary, PLV2K copolymer has striking functions such as uncompetitive P-gp ATPase reversible inhibitor and anticancer efficacy, and could be a promising nanocarrier in improving the chemotherapy of hydrophobic anticancer drugs.
Related Topics
Physical Sciences and Engineering
Chemical Engineering
Bioengineering
Authors
Jinling Wang, Jin Sun, Qin Chen, Ying Gao, Lin Li, Hui Li, Donglei Leng, Yongjun Wang, Yinghua Sun, Yongkui Jing, Siling Wang, Zhonggui He,