Purpose: Photothermal therapy (PTT) is a promising anticancer treatment that involves inducing thermal ablation and enhancing antitumor immune responses. However, it is difficult to completely eradicate tumor foci through thermal ablation alone. Additionally, the PTT elicited antitumor immune responses are often insufficient to prevent tumor recurrence or metastasis, due to the presence of an immunosuppressive microenvironment. Therefore, combining photothermal and immunotherapy is believed to be a more effective treatment approach as it can modulate the immune microenvironment and amplify the post-ablation immune response.
Methods: Herein, the indoleamine 2, 3‐dioxygenase‐1 inhibitors (1-MT) loaded copper (I) phosphide nanocomposites (Cu₃P/1-MT NPs) are prepared for PTT and immunotherapy. The thermal variations of the Cu₃P/1-MT NPs solution under different conditions were measured. The cellular cytotoxicity and immunogenic cell death (ICD) induction efficiency of Cu₃P/1-MT NPs were analyzed by cell counting kit-8 assay and flow cytometry in 4T1 cells. And the immune response and antitumor therapeutic efficacy of Cu₃P/1-MT NPs were evaluated in 4T1-tumor bearing mice.
Results: Even at low energy of laser irradiation, Cu₃P/1-MT NPs remarkably enhanced PTT efficacy and induced immunogenic tumor cell death. Particularly, the tumor-associated antigens (TAAs) could help promote the maturation of dendritic cells (DCs) and antigen presentation, which further activates infiltration of CD8⁺ T cells through synergistically inhibiting the indoleamine 2, 3‐dioxygenase‐1. Additionally, Cu₃P/1-MT NPs decreased the suppressive immune cells such as regulatory T cells (Tregs) and M2 macrophages, indicating an immune suppression modulation effect.
Conclusion: Cu₃P/1-MT nanocomposites with excellent photothermal conversion efficiency and immunomodulatory properties were prepared. In addition to enhanced the PTT efficacy and induced immunogenic tumor cell death, it also modulated the immunosuppressive microenvironment. Thereby, this study is expected to offer a practical and convenient approach to amplify the antitumor therapeutic efficiency with photothermal-immunotherapy.
Keywords: copper (I) phosphide (Cu₃P), photothermal therapy, IDO‐1 inhibitors, immunotherapy