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課題組關于熱和pH雙重可控電荷反轉的接枝共聚物膠束在克服癌細胞抗藥性方面的研究發表在J. Mater. Chem. B上

Thermo and pH Dual-Controlled Charge Reversal Amphiphilic Graft Copolymer Micelles for Overcoming Drug Resistance in Cancer Cells

Haitao Zhang,aXiao-dong Fan,a,*Fei Li,bRongtian Suo,aHui Li,aZhen Yang,aWanbin Zhang,aYang Bai,cWei Tian,a,*

Currently, multidrug resistance (MDR) is the major challenge of nanotechnology in cancer treatment. In this study, a series of amphiphilicpoly(styrene-co-maleic anhydride)-graft-poly(2-(N,N-dimethylamino)ethyl methacrylate) graft copolymer [PSMA89-g-P(DMA16-co-SD)] micelles, was 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 property 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 °C to 37 °C at pH 7.4. However, when the pH value was adjusted to 6.8 at 37 °C, 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 °C among those with pH 7.4 at 37 °C and pH 7.4 at 25 °C, leading to higher efficiency in overcoming MDR of A2780/DoxRcells. Therefore, PSMA89-g-P(DMA16-co-SD56) micelles can be used as intelligent drug-delivery systems to overcome MDR of cancercells.

全文鏈接:http://pubs.rsc.org/en/Content/ArticleLanding/2015/TB/C5TB00530B#!divAbstract

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