Targeted Nanophotoimmunotherapy Potentiates Cancer Treatment by Enhancing Tumor Immunogenicity and Improving the Immunosuppressive Tumor Microenvironment.

Cancer immunotherapy, such as immune checkpoint blockade, chimeric antigen receptor, and cytokine therapy, has emerged as a robust therapeutic strategy activating the host immune system to inhibit primary and metastatic lesions. However, low tumor immunogenicity (LTI) and immunosuppressive tumor microenvironment (ITM) severely compromise the killing effect of immune cells on tumor cells, which fail to evoke a strong and effective immune response. As an exogenous stimulation therapy, phototherapy can induce immunogenic cell death (ICD), enhancing the therapeutic effect of tumor immunotherapy. However, the lack of tumor targeting and the occurrence of immune escape significantly reduce its efficacy in vivo , thus limiting its clinical application. Nanophotoimmunotherapy (nano-PIT) is a precision-targeted tumor treatment that co-loaded phototherapeutic agents and various immunotherapeutic agents by specifically targeted nanoparticles (NPs) to improve the effectiveness of phototherapy, reduce its phototoxicity, enhance tumor immunogenicity, and reverse the ITM. This review will focus on the theme of nano-PIT, introduce the current research status of nano-PIT on converting "cold" tumors to "hot" tumors to improve immune efficacy according to the classification of immunotherapy targets, and discuss the challenges, opportunities, and prospects.