Multifunctional nanoparticles precisely reprogram the tumor microenvironment and potentiate antitumor immunotherapy after near-infrared-II light-mediated photothermal therapy

• DOI: 10.1016/j.actbio.2023.05.051
• Publication Date: 2023-06-10T17:48:27Z
• Authors: Yanni Ge; Jiaojiao Zhang; Kai Jin; Ziqiang Ye; Wei Wang; Zhuxian Zhou; Juan Ye
• Keywords: Photothermal Therapy; Ovalbumin; Multifunctional Nanoparticles; Hyperthermia, Induced; Phototherapy; Sulfides; 3. Good health; Mice; Neoplasms; Cell Line, Tumor; Tumor Microenvironment; Animals; Nanoparticles; Immunotherapy; Immune Checkpoint Inhibitors; Copper

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.