纳米医学
坏死性下垂
癌细胞
癌症研究
结直肠癌
阿霉素
癌症
转移
细胞凋亡
材料科学
自噬
药物输送
程序性细胞死亡
药理学
生物物理学
化学
纳米技术
生物化学
生物
医学
化疗
纳米颗粒
内科学
作者
Xiaoling Li,Zhenyu Duan,Xiaoting Chen,Dayi Pan,Kui Luo,Lei Gu,Gang Xu,Yinggang Li,Hu Zhang,Qiyong Gong,Rongjun Chen,Zhongwei Gu,Kui Luo
标识
DOI:10.1002/adma.202300548
摘要
Targeting metabolic vulnerability of tumor cells is a promising anticancer strategy. However, the therapeutic efficacy of existing metabolism-regulating agents is often compromised due to tolerance resulting from tumor metabolic plasticity, as well as their poor bioavailability and tumor-targetability. Inspired by the inhibitive effect of N-ethylmaleimide on the mitochondrial function, a dendronized-polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating maleimide-modified doxorubicin (Mal-DOX) is developed to enable improvement in the overall delivery efficiency and inhibition of the tumor metabolism via multiple pathways. It is observed that Mal-DOX and its derived nanomedicine induces energy depletion of CT26 colorectal cancer cells more efficiently than doxorubicin, and shifts the balance of programmed cell death from apoptosis toward necroptosis. Notably, pOEG-b-D-SH@NP simultaneously inhibits cellular oxidative phosphorylation and glycolysis, thus potently suppressing cancer growth and peritoneal intestinal metastasis in mouse models. Overall, the study provides a promising dendronized-polymer-derived nanoplatform for the treatment of cancers through impairing metabolic plasticity.
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