2. Academic Validation
  3. Attenuating Metabolic Competition of Tumor Cells for Favoring the Nutritional Demand of Immune Cells by a Branched Polymeric Drug Delivery System

Attenuating Metabolic Competition of Tumor Cells for Favoring the Nutritional Demand of Immune Cells by a Branched Polymeric Drug Delivery System

  • Adv Mater. 2022 Dec 11;e2210161. doi: 10.1002/adma.202210161.
Yinggang Li 1,  Zhenyu Duan 1,  Dayi Pan 1,  Long Ren 1,  Lei Gu 1,  Xiaoling Li 1,  Gang Xu 1 2,  Hongyan Zhu 1,  Hu Zhang 3,  Zhongwei Gu 1,  Rongjun Chen 4,  Qiyong Gong 1 2 5,  Yao Wu 1,  Kui Luo 1 2
Affiliations

Affiliations

  • 1 Huaxi MR Research Center (HMRRC), Department of Radiology, Frontiers Science Center for Disease-Related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, and National Engineering Research Center for Biomaterials, 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 Chemical Engineering, Imperial College London, South Kensington Campus, London, SW7 2AZ, UK.
  • 5 Department of Radiology, West China Xiamen Hospital of Sichuan University, Xiamen, Fujian, 361000, China.
PMID: 36504170 DOI: 10.1002/adma.202210161
Abstract

Tumor cells are dominant in the nutritional competition in the tumor microenvironment, and their metabolic abnormalities often lead to microenvironmental acidosis and nutrient deprivation, thereby impairing the function of immune cells and diminishing the antitumor therapeutic effect. Herein, a branched polymeric conjugate and its efficacy in attenuating the metabolic competition of tumor cells are reported. Compared with the control nanoparticles prepared from its linear counterpart, the branched-conjugate-based nanoparticles can more efficiently accumulate in the tumor tissue and interfere with the metabolic processes of tumor cells to increase the concentration of essential nutrients and reduce the level of immunosuppressive metabolites in the TME, thus creating a favorable environment for infiltrated immune cells. Its combined treatment with an Immune Checkpoint Inhibitor (ICI) achieves an enhanced antitumor effect. The work presents a promising approach for targeting metabolic competition in the TME to enhance the chemo-immunotherapeutic effect against cancers.

Keywords

branched polymeric prodrug conjugates; chemo-immunotherapy; immunogenic cell death; metabolic competition; tumor immune microenvironment.

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