CuS Nanoparticles-mediated Tumor Hyperthermia Combines Immunotherapy

Nanomaterial-mediated tumor photothermia(PTT)has attracted widespread attention among researchers.The basic principle of tumor photothermia is that the photothermia agents accumulated in the tumor site,which can absorb the near-infrared light and convert it to a high temperature higher than 45?,leading to the destruction of tumor tissues,causing death and apoptosis of tumors.It has 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).During the tumor tissues receive photothermal therapy,tumor-associated antigens must release in the tumor microenvironment,which can adsorb by CuS NPs,then the antigens will further induce the body's immune response through the action of tumor-draining lymph nodes,in combination with immunosuppressant,anti-PD-L1,to achieve the purpose of curing tumors.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,photothermal therapy mediated by CuS NPs-PEG-Mal enhanced the number of tumor-infiltrating CD8~+T cells,CD3~+CD45~+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.