課題組關(guān)于熱和pH雙重可控電荷反轉(zhuǎn)的接枝共聚物膠束在克服癌細(xì)胞抗藥性方面的研究發(fā)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