Semiconducting Polymer Nano-regulators with Cascading Activation for Photodynamic Cancer Immunotherapy

  • Angew Chem Int Ed Engl. 2022 Mar 1;61(10):e202116669. doi: 10.1002/anie.202116669.
Shasha He  1 ,  Jing Liu  2  3  4  5 ,  Chi Zhang  1 ,  Jun Wang  2  3  4  5 ,  Kanyi Pu  1  6  7
Affiliations
  • 1. School of Chemical and Biomedical Engineering, Nanyang Technological University, 70 Nanyang Drive, Singapore, 637457, Singapore.
  • 2. School of Biomedical Sciences and Engineering, Guangzhou International Campus, South China University of Technology, Guangzhou, 510006, P. R. China.
  • 3. National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
  • 4. Key Laboratory of Biomedical Engineering of Guangdong Province, and Innovation Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, P. R. China.
  • 5. Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, P. R. China.
  • 6. School of Physical and Mathematical Sciences, Nanyang Technological University, Singapore, 637371, Singapore.
  • 7. Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 636921, Singapore.
PMID: 34967097 DOI: 10.1002/anie.202116669
Abstract

Combination photoimmunotherapy holds promise for tumor suppression; however, smart phototherapeutic agents that only activate their immune pharmaceutical action in tumors have been rarely developed. Herein, we report a semiconducting polymer (SP) nano-regulator (SPNT ) with cascading activation for combinational photodynamic Cancer Immunotherapy. SPNT comprises an immunoregulator (M-Trp: 1-methyltryptophan) conjugating to the side chain of the SP backbone via an apoptotic biomarker-cleavable linker. Under near-infrared photoirradiation, SPNT produces singlet oxygen to induce immunogenic Apoptosis. Concurrently, an apoptotic biomarker is upregulated, which triggers the specific cleavage of M-Trp for indoleamine 2,3-dioxygenase (IDO) activity inhibition, regulatory T cells reduction and cytotoxic T lymphocytes infiltration. SPNT -mediated combination photodynamic immunotherapy thus reprograms the tumor immune microenvironment, resulting in efficient suppression of tumors, and inhibition of lung metastasis.

Keywords
Apoptotic Biomarker; Cancer Therapy; Cascading Activation; Immunotherapy; Photodynamic Therapy.
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