Mechanism of selenium-doped black phosphorus nanosheets wrapped with biomimetic tumor cell membrane for prostate cancer immunotherapy

Prostate cancer (PCa) is commonly considered a “cold tumor” due to its immunosuppressive microenvironment. Cold tumors are typically identified by the absence of T-cell infiltration within the tumor, while other immune populations and myeloid cells can be observed in these tumors. To achieve light-heat combined immunotherapy checkpoint inhibitor treatment for castration-resistant prostate cancer, we aimed to transforming “cold tumors” into “hot tumors”. We designed and synthesized a two-dimensional material, selenium-doped black phosphorus (BP), to enhance the photothermal conversion efficiency, and formed Se@BPNSs by liquid-phase exfoliation. To address the issue of enhanced permeability and retention effect, and to achieve efficient targeting, we coated the Se@BPNSs with RM-1 cell membrane derived from mouse prostate cancer cells. By injecting a certain dose of Se@BPNSs into the tumor and irradiating with a 808 nm laser, the Se@BPNSs converted light energy into heat to kill tumor cells at high temperatures while releasing antigens captured by dendritic cells. In addition, we combined the immunotherapy checkpoint inhibitor anti-PD1 to enhance the immune response and promote immune cell infiltration. The successful preparation of Se@BPNSs was verified through material characterization, cell-level and animal-level experiments, and the antitumor effect was meanwhile verified, which further provided guidance for prostate cancer treatment by photothermal synergistic immunotherapy.