Self-assembly nanoparticles potentiate in-situ tumor vaccine of radiotherapy by regulating tumor immunogenicity and tumor-associated macrophages

Radiotherapy can release personalized in-situ tumor vaccines, thereby potentiating adaptive immune responses. However, due to the low immunogenicity of tumor cells and the immunosuppressive microenvironment, these vaccines cannot effectively be presented and activate the immune system. Here, we designed self-assembling nanoparticles (AZ-NPs) using all-trans retinoic acid (ATRA) and zoledronic acid (Zol) to enhance the immune response of radiotherapy-induced in-situ tumor vaccine. Within the AZ-NPs, ATRA can increase the expression of tumor antigens and MHC-I molecules to release more tumor antigens through radiotherapy, while Zol can eliminate immunosuppressive tumor-associated macrophages, thereby enhancing the in-situ tumor vaccine presentation of DCs. Through the combination of AZ-NPs and radiotherapy, a robust synergistic antitumor immune response was achieved, including a significant increase in mature DCs, CD8+ T cells, and memory T cells. More importantly, this combined strategy can induce long-term immune memory to suppress tumor recurrence and metastasis. Overall, our findings provide a feasible strategy for activating the systemic immune response of radiotherapy.