NIR-II light-driven in situ nanovaccine for cancer immunotherapy via lymph node migration-mediated accumulation

Background: Tumor vaccines that combine tumor antigens with immune adjuvants offer a promising strategy for cancer immunotherapy. A particularly effective approach involves the in situ generation of tumor antigens within the tumor microenvironment and their subsequent delivery to the lymph nodes alongside immune adjuvants. However, Co-delivery of antigen and adjuvant on a single nano-platform remains facing some key problems, such as a single nanomedicine cannot simultaneously achieve antigen production, capture, and delivery to lymph nodes, as well as leakage of adjuvant due to destruction of nano-drug by exogenous stimuli and failure to capture antigen effectively. Methods: To address this, this study develops two synergistic nanodrugs: AuP and VNP_R848. Under 1064 nm laser irradiation, AuP generates many tumor antigens, whereas VNP_R848, distinguished by its small size and high viscosity, captures these autologous antigens and encapsulates the immune adjuvant R848. Results: This combination creates an in situ cancer nanovaccine capable of lymph node migration. Nanovaccines enhance dendritic cell uptake and maturation, promoting antigen processing and presentation to T cells, which triggers a robust antitumor immune response. Remarkably, the nanovaccine we developed demonstrated superior therapeutic efficacy in distal tumors, postoperative recurrence and pulmonary metastatic tumor models, while also inducing long-term immune memory. Conclusion: This study presents a straightforward and effective strategy for developing in situ nanovaccines for cancer immunotherapy, with wide-ranging clinical application prospects.