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 VNPR848.Under 1064 nm laser irradiation, AuP generates many tumor antigens, whereas VNPR848, 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.