生物物理学
线粒体
线粒体内膜
纳米医学
胞浆
乙二醇
癌细胞
内体
硫酸软骨素
细胞凋亡
化学
细胞色素c
聚合物囊泡
细胞
纳米颗粒
材料科学
纳米技术
生物化学
聚合物
两亲性
生物
癌症
共聚物
糖胺聚糖
有机化学
遗传学
酶
作者
Xiaobin Zhang,Yi Wang,Guoqing Wei,Jingya Zhao,Guang Yang,Shaobing Zhou
标识
DOI:10.1016/j.jconrel.2020.03.011
摘要
Methods to selectively destroy mitochondria of tumor cells and induce cell apoptosis with nanomedicine constitute challenges in cancer therapy. In the present study, we develop cell membrane/mitochondria dual targeting and pH/redox dual responsive nanoparticles for mitochondrion therapy. The nanoparticles are fabricated by the self-assembly of triphenylphosphonium (TPP) grafted poly(ethylene glycol)(PEG)-poly(d,l-lactide)(PLA) copolymers (TPP-PEG-ss-PLA) using disulfide bonds as the intermediate linkers. To shield the surface positive charge of the nanoparticles from TPP composition, chondroitin sulfate (CS) is employed to coat the nanoparticles, and this prolongs blood circulation while endowing an active targeting ability to the cell membrane. In acidic lyso-somes/endosomes, the negatively charged CS layer falls away to expose the TPP component. Subsequently, in the cyto-plasm, the nanoparticles can anchor to the mitochondrial outer membrane by TPP-mediated targeting, thereby inducing a decrease in the membrane potential and opening of the permeability transition pore. Thus, the overproduction of ROS in the mitochondria promotes cell apoptosis. The released DOX directly diffuse into the mitochondria, thereby resulting in mito-chondrial DNA damage. Therefore, the nanoparticles exhibit significant potential in terms of a new avenue for mitochondrion therapy in cancer treatment.
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