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Impairing Tumor Metabolic Plasticity Via a Stable Metal-Phenolic Based Polymeric Nanomedicine to Suppress Colorectal Cancer

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机构： [1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Functional and molecular imaging Key Laboratory of Sichuan Province, Key Laboratory of Transplant Engineering and Immunology, NHC, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China. [3]Amgen Bioprocessing Centre, Keck Graduate Institute, Claremont, CA, 91711, USA. [4]Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, 361000, China. [5]Department of Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, United Kingdom.

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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.This article is protected by copyright. All rights reserved.

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出版当年[2023]版：

大类 | 1 区

材料科学

小类 | 1 区化学：综合 1 区物理化学 1 区材料科学：综合 1 区纳米科技 1 区物理：应用 1 区物理：凝聚态物理

最新[2023]版：

大类 | 1 区

材料科学

小类 | 1 区化学：综合 1 区物理化学 1 区材料科学：综合 1 区纳米科技 1 区物理：应用 1 区物理：凝聚态物理

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第一作者机构： [1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China.

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通讯作者：

通讯机构： [1]Huaxi MR Research Center (HMRRC), Animal Experimental Center, Department of Radiology, National Clinical Research Center for Geriatrics, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, China. [2]Functional and molecular imaging Key Laboratory of Sichuan Province, Key Laboratory of Transplant Engineering and Immunology, NHC, and Research Unit of Psychoradiology, Chinese Academy of Medical Sciences, Chengdu, 610041, China.

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