Impairing Tumor Metabolic Plasticity via a Stable Metal‐Phenolic‐Based Polymeric Nanomedicine to Suppress Colorectal Cancer

Autor: Xiaoling Li, Zhenyu Duan, Xiaoting Chen, Dayi Pan, Qiang Luo, Lei Gu, Gang Xu, Yinggang Li, Hu Zhang, Qiyong Gong, Rongjun Chen, Zhongwei Gu, Kui Luo
Rok vydání: 2023
Předmět:
Zdroj: Advanced Materials.
ISSN: 1521-4095
0935-9648
Popis: Targeting metabolic vulnerability of tumor cells is a promising anti-cancer 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, we developed a dendronized polymer-functionalized metal-phenolic nanomedicine (pOEG-b-D-SH@NP) encapsulating N-ethylmaleimide-modified doxorubicin (Mal-DOX) to enable improvement in the overall delivery efficiency and inhibition of the tumor metabolism via multiple pathways. We observe that Mal-DOX and its derived nanomedicine induce 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 nano-platform for the treatment of cancers through impairing metabolic plasticity. This article is protected by copyright. All rights reserved.
Databáze: OpenAIRE
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