Surface Functionalized Modified Copper Sulfide Nanoparticles Enhance Checkpoint Blockade Tumor Immunotherapy by Photothermal Therapy and Antigen-Capturing.

Nano-material-based tumor photothermal therapy (PTT) has attracted increasing attention and been a promising method for cancer treatment due to its low level of adverse effects and noninvasiveness. However, thermotherapy alone still cannot control tumor metastasis and recurrence. Here, we developed surface functionalized modified copper sulfide nanoparticles (CuS NPs). CuS NPs can not only be used as photothermal mediator for tumor hyperthermia, but also can adsorb tumor antigens released during hyperthermia as an antigen-capturing agent to induce antitumor immune response. We selected maleimide polyethylene glycol modified CuS NPs (CuS NPs-PEG-Mal) with stronger antigen adsorption capacity, in combination with immune checkpoint blocker (anti-PD-L1) to evaluate the effect of hyperthermia improving immunotherapy in 4T1 breast cancer tumor model. The results showed hyperthermia based on CuS NPs-PEG-Mal distinctly increased the levels of inflammatory cytokines in serum, leading to tumor immunogenic microenvironment. In combination with anti-PD-L1, photothermal therapy mediated by CuS NPs-PEG-Mal enhanced the number of tumor-infiltrating CD8+ T cells, inhibited the growth of primary tumors and distant tumors in 4T1 tumor model. The therapeutic strategies provide a simple and effective treatment option for metastatic and recurrent tumors.