Second Near‐Infrared Light‐Activatable Polymeric Nanoantagonist for Photothermal Immunometabolic Cancer Therapy

• Published in: Advanced materials (Weinheim) Vol. 33; no. 36; pp. e2101410 - n/a
• Main Authors: Xu, Cheng, Jiang, Yuyan, Huang, Jingsheng, Huang, Jiaguo, Pu, Kanyi
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 01.09.2021
• Subjects: Ablation; Adenosine; Animals; Apoptosis - radiation effects; Cancer; cancer therapy; Caspase 3 - metabolism; Cell death; Cell Line, Tumor; Humans; Hyperthermia, Induced; Immunology; Immunomodulators; Immunotherapy; Infrared Rays; Lymphocytes; Materials science; Mice; Nanostructures - chemistry; Near infrared radiation; Neoplasms - radiotherapy; photoactivation; Photothermal Therapy; polymer nanoparticles; Polymers - chemistry; Remote control; second near‐infrared photothermal therapy; Semiconductors; Signal Transduction; T-Lymphocytes, Cytotoxic - drug effects; Theranostic Nanomedicine; Tumors; cancer therapy; polymer nanoparticles; photoactivation; second near-infrared photothermal therapy
• ISSN: 0935-9648; 1521-4095
• DOI: 10.1002/adma.202101410

Immunometabolic modulation offers new opportunities to treat cancers as it is highly associated with cancer progression and immunosuppressive microenvironment. However, traditional regimens using nonselective small‐molecule immunomodulators lead to the off‐target adverse effects and insufficient therapeutic outcomes. Herein a second near‐infrared (NIR‐II) photothermally activatable semiconducting polymeric nanoantagonist (ASPA) for synergistic photothermal immunometabolic therapy of cancer is reported. ASPA backbone is obtained by conjugating vipadenant, an antagonist to adenosine A2A receptor, onto NIR‐II light‐absorbing semiconducting polymer via an azo‐based thermolabile linker. Under deep‐penetrating NIR‐II photoirradiation, ASPA induces tumor thermal ablation and subsequently immunogenic cell death, triggers the cleavage of thermolabile linker, and releases the antagonist to block the immunosuppressive adenosinergic pathway. Such a remotely controlled immunometabolic regulation potentiates cytotoxic T cell functions while suppresses regulatory T cell activities, leading to efficient primary tumor inhibition, pulmonary metastasis prevention, and long‐term immunological memory. Thereby, this work provides a generic polymeric approach for precise spatiotemporal regulation of cancer immunometabolism. A photoactivatable semiconducting polymeric nanoantagonist (ASPA) is presented, whose photothermal and immunomodulation activities are controlled by second near‐infrared light. Such a design can not only elicit tumor ablation and immunogenic cell death, but also initiate immunometabolic reprogramming on the adenosinergic pathway, thereby fostering tumoricidal cytotoxic T cells yet counteracting the immunosuppressive Treg cells in tumor.