2. Academic Validation
  3. Platinum(IV) complexes as inhibitors of CD47-SIRPα axis for chemoimmunotherapy of cancer

Platinum(IV) complexes as inhibitors of CD47-SIRPα axis for chemoimmunotherapy of cancer

  • Eur J Med Chem. 2022 Feb 5;229:114047. doi: 10.1016/j.ejmech.2021.114047.
Yehong Tan 1,  Hanhua Chen 1,  Jie Zhang 1,  Linxiang Cai 1,  Suxing Jin 2,  Dongfan Song 2,  Tao Yang 3,  Zijian Guo 4,  Xiaoyong Wang 5
Affiliations

Affiliations

  • 1 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, PR China.
  • 2 State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China.
  • 3 State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China. Electronic address: yangtao1991@nju.edu.cn.
  • 4 State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, PR China; Nanchuang (Jiangsu) Institute of Chemistry and Health, Jiangbei New Area, Nanjing, 210000, PR China.
  • 5 State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, PR China; Nanchuang (Jiangsu) Institute of Chemistry and Health, Jiangbei New Area, Nanjing, 210000, PR China. Electronic address: boxwxy@nju.edu.cn.
PMID: 34915428 DOI: 10.1016/j.ejmech.2021.114047
Abstract

Phagocytosis of Cancer cells by antigen presenting cells (APCs) is critical to activate the host's immune responses. However, the targeting ability of APCs to Cancer cells is limited by the upregulation of transmembrane protein CD47 on the Cancer cell surface. Blocking CD47 can affect the macrophage-mediated phagocytosis. Two platinum-based immunomodulators MUP and DMUP were synthesized to enhance the phagocytic activity of macrophages by blocking the CD47-SIRPα axis. These PtIV complexes not only showed high antiproliferative activity against a panel of human Cancer cell lines, but also cooperated with human peripheral blood mononuclear cells (PBMCs) to suppress Cancer cells. They acted as Immune Checkpoint inhibitors to modulate the immune responses of both Cancer and immune cells. In particular, DMUP decreased the expression of CD47 in tumor tissues and promoted the polarization of macrophages from M2 to M1 phenotype in a mouse model of non-small cell lung Cancer, thereby enhancing the Anticancer effect. By interfering with DNA synthesis and stimulating immune system, DMUP takes the advantage of chemotherapy and immunotherapy to inhibit Cancer cells. The dual efficacy of DMUP makes it a potential chemoimmunotherapeutic agent in Cancer therapy.

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Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-115983
    ≥98.0%, CD47-SIRPα axis Inhibitor