Engineering a Self-DeliveryNanoplatform for Chemo-Photodynamic-ImmuneSynergistic Therapies against Aggressive Melanoma

The effectiveness of immunotherapy in killing melanoma is hindered by a T-cell deficiency and the lack of tumor immunogenicity. Consequently, there is an urgent need for a platform that can further activate the immune system and boost the immune response of the host to tumors. Compared with monotherapy, combination therapy shows promise in improving treatment efficacy and response rates. This study introduces the pioneering use of a rationally designed active targeting nanoplatform to bind axitinib, paclitaxel, and verteporfin to human serum albumin (APV@HSA NPs). APV@HSA NPs have demonstrated the capability to induce dual-induced apoptosis in tumor cells through chemo- and photodynamic effects, while also enhancing immunogenic cell death and promoting dendritic cell maturation. Additionally, the platform promoted the production of CD8⁺ T cells and memory T cells and inhibited vascular endothelial growth factor via axitinib, facilitating the infiltration of immune effector cells and optimizing chemo-photodynamic immunotherapy. Hence, amplified chemo-photodynamic-immunological nanomedicines with excellent biocompatibility have been redesigned to inhibit the tumor microenvironment and combat the growth of primary tumor and lung metastasis. This approach initiates a series of immune responses, presenting a promising therapeutic strategy for melanoma.