An injectable, dual-crosslinked polypeptide hydrogel encapsulating resiquimod-loaded nanoparticles as a long-lasting...

Cancer immunotherapy is an emerging therapeutic approach that demonstrates superior immune specificity and reduced off-target effects compared to conventional chemotherapy, radiotherapy and surgery. Cancer vaccines are a promising immunotherapeutic strategy, though their clinical application faces limitations including inefficient antigen presentation, inadequate immunogenicity, and failure to establish an effective, durable immune microenvironment in vivo. To address these issues, we developed a physically and chemically dual-crosslinked hydrogel vaccine delivery system. Leveraging its unique differential degradation properties, this system enabled the sustained release of three critical immunostimulants, including tumor antigens, granulocyte macrophage-colony stimulating factor, and resiquimod-loaded nanoparticles. Simultaneously, it formed a three-dimensional scaffold at the injection site with dynamically expanding porous structures induced by degradation. This efficiently recruited and reprogramed innate immune cells. This hydrogel vaccine established a long-lasting immune activating site at the injection site. In both prophylactic and post-surgical tumor recurrence models, the gel vaccine successfully induced significant and sustained antigen-specific immune responses, effectively suppressing tumor growth. This study developed an in situ immune cell reprogramming cancer vaccine capable of providing long-term immune protection against tumor growth and recurrence.