In Situ Photothermal Activation of Necroptosis Potentiates Black Phosphorus-Mediated Cancer Photo-Immunotherapy

Abstract

Abstract Photo-immunotherapy taking advantages of the immunogenic cell death (ICD) induced by photothermal therapy (PTT) to facilitate the systemic anti-tumor immunity has been exploited as a promising therapeutic approach for cancer. However, this kind of in situ tumor vaccine is of less efficacy due to the anisotropic immunogenicity profiles of dying cells after PTT. Herein, a facile strategy is proposed to activate the necroptosis, a programmed cell death with intense immunogenicity, in photothermal ablated cells by easily modulating the PTT parameters, which enables the optimal ICD for anti-tumor immunity. As an emerging 2D nanomaterial, black phosphorus (BP) serves as the near-infrared (NIR)-responsive nanoagent to trigger PTT. Necroptosis in ablated tumor cells is confirmed by the high expression of key proteins in necroptotic pathway. The necroptotic cells also exhibit considerable immunogenicity by the release of damage-associated molecular patterns to potentiate the immune responses. Further an immunologic adjuvant is grafted onto the BP nanosheets and the high-performance cancer photo-immunotherapy is achieved. This easy-to-access photo-immunotherapeutic strategy by in situ photothermal activation of necroptosis supplies new insights in the treatment of cancer.