2. Academic Validation
  3. Impairing Tumor Metabolic Plasticity via a Stable Metal-Phenolic-Based Polymeric Nanomedicine to Suppress Colorectal Cancer

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

  • Adv Mater. 2023 Mar 14;e2300548. doi: 10.1002/adma.202300548.
Xiaoling Li 1,  Zhenyu Duan 1,  Xiaoting Chen 1,  Dayi Pan 1,  Qiang Luo 1,  Lei Gu 1,  Gang Xu 1 2,  Yinggang Li 1,  Hu Zhang 3,  Qiyong Gong 1 2 4,  Rongjun Chen 5,  Zhongwei Gu 1,  Kui Luo 1 2
Affiliations

Affiliations

  • 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, UK.
PMID: 36917817 DOI: 10.1002/adma.202300548
Abstract

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.

Keywords

dendronized polymer; glycolysis; nanomedicine; oxidative phosphorylation; tumor metabolic plasticity.

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