铜
纳米医学
化学
细胞内
生物物理学
纳米颗粒
体内
谷胱甘肽
生物化学
组合化学
纳米技术
材料科学
生物
有机化学
酶
生物技术
作者
Qinghua Wang,Xianglong Li,Jiayi Mao,Xing Qin,Shaobo Yang,Ji‐Na Hao,Min Guan,Yuanyuan Cao,Yongsheng Li
标识
DOI:10.1002/adhm.202101634
摘要
In eukaryotes and prokaryotes, some copper transportations driven by gradient copper-binding affinities exhibit typical glutathione (GSH)-responsive features. Inspired by these delicate endogenous processes, a biomimic copper-ion mediated GSH-responsive nanomedicine is designed based on the gradient copper-binding strengths between polydopamine (PDA) species and GSH. The nanomedicine is constructed as core-shell nanoparticles with copper-polydopamine (Cu-PDA) coordinated shell and micellar core encapsulating chemotherapeutic drug of β-lapachone (β-lapa). In tumor cells, the excess intracellular GSH will reduce and extract the Cu(II) from the Cu-PDA network, triggered by the binding affinity gradients between Cu-PDA and Cu-GSH, resulting in the breaking of the shell and the releasing of β-lapa and Fenton agent copper. The additional Fenton reaction of copper ions induces excess oxidative damage of tumor cells assisted by the abundant H2 O2 amplified by β-lapa, achieving cascade anticancer effects combining chemodynamic therapy with chemotherapy. This multilevel anticancer system exhibits an efficient tumor inhibitory rate and a negligible systematic toxicity for normal organs in vivo, presenting a new bioinspired GSH-responsive strategie to develop stimuli-responsive structures.
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