Multifunctional Nanoparticles Precisely Reprogram the Tumor Microenvironment and Potentiate Antitumor Immunotherapy after Near-Infrared-II Light-Mediated Photothermal Therapy.

Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy. However, mild PTT alone usually fails to activate the immune response and prevent tumor metastasis. Herein, a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an effective PTT effect in the second near-infrared (NIR-II) window, is developed. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response. Copper ions are released in the acidic TME to promote the M1 polarization of tumor-associated macrophages. The model antigen OVA not only acts as a scaffold for nanoparticle growth but also promotes the maturation of dendritic cells, which primes naive T cells to stimulate adaptive immunity. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, which suppresses tumor growth and metastasis in a mouse melanoma model. The proposed therapeutic platform, CuS@OVA nanoparticles, may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies. STATEMENT OF SIGNIFICANCE: Mild-temperature photothermal therapy (mild PTT) is a safe and efficient antitumor therapy, but usually fails to activate the immune response and prevent tumor metastasis. Herein, we develop a photothermal agent, copper sulfide@ovalbumin (CuS@OVA), with an excellent PTT effect in the second near-infrared (NIR-II) window. CuS@OVA can optimize the tumor microenvironment (TME) and evoke an adaptive immune response by promoting the M1 polarization of tumor-associated macrophages and the maturation of dendritic cells. CuS@OVA augments the antitumor efficiency of the immune checkpoint blockade (ICB) in vivo, suppressing tumor growth and metastasis. The platform may be a potential adjuvant for optimizing the TME and improving the efficiency of ICB as well as other antitumor immunotherapies.