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[J. Mater. Chem. B] Thermo and pH dual-controlled charge reversal amphiphilic graft copolymer micelles for overcoming drug resistance in cancer cells
作者:Haitao Zhang,Xiaodong Fan,*Fei Li,Rongtian Suo,Hui Li,Zhen Yang,Wanbin Zhang,Yang Bai,Wei Tian*
關鍵字:charge reversal,amphiphilic graft copolymer micelles,drug resistance
論文來源:期刊
具體來源:J. Mater. Chem. B, 2015, 3, 4585--4596
發表時間:2015年
Currently, multidrug resistance (MDR) is the major challenge of nanotechnology in cancer treatment. In this study, a series of amphiphilic poly(styrene-co-maleic anhydride)-graft-poly(2-(N,N-dimethylamino)ethyl methacrylate) graft copolymer [PSMA89-g-P(DMA16-co-SD)] micelles were prepared. PSMA89-g-P(DMA16-co-SD) graft copolymers were first synthesized by grafting different amounts of sulfadimethoxine (SD) onto PSMA89-g- P(DMA16-co-SD). The PSMA89-g-P(DMA16-co-SD56) micelles exhibited a thermo and pH dual-controlled charge reversal properties without cleavage of chemical bonds. The surface charge of PSMA89-g-P(DMA16-co-SD56) micelles reversed from positive to negative after the solution temperature increased from 25 1C to 37 1C at pH 7.4. However, when the pH value was adjusted to 6.8 at 37 1C, the surface charge became positive again. The thermo and pH dual-controlled charge reversal not only resulted in a controlled doxorubicin (DOX) release but also effectively enhanced the cellular uptake of DOX-loaded PSMA89-g-P(DMA16-co-SD56) micelles through electrostatic absorptive endocytosis. MTT assay demonstrated that DOX-loaded PSMA89-g-P(DMA16-co-SD56) micelles showed the highest inhibition growth of DOX-resistant ovarian carcinoma (A2780/DoxR) cells with pH 6.8 at 37 1C among those with pH 7.4 at 37 1C and pH 7.4 at 25 1C, leading to higher efficiency in overcoming MDR of A2780/DoxR cells. Therefore, PSMA89-g-

P(DMA16-co-SD56) micelles can be used as intelligent drug-delivery systems to overcome MDR of cancer cells.

全文鏈接:http://pubs.rsc.org/en/content/articlelanding/2015/tb/c5tb00530b#!divAbstract

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