An antigen-capturing and lymph node-targeting nanoparticle for cancer immunotherapy

Cancer immunotherapy leverages the immune system to combat cancer and has shown promise for many patients. However, its effectiveness is often hampered by an immunosuppressive tumor microenvironment and the low immunogenicity of tumor cells. In this study, we developed an in situ cancer vaccine that integrates chemotherapy and immunotherapy in a single platform. We synthesized two amphiphilic polymers with polyalbumin-binding domains (PABD) that can target the lymph nodes, PABD-PGEA and PABD-PGED. Compared with previous albumin-hijacking strategies utilizing the same albumin-binding domains, PABD-PGEA exhibited approximately six times greater lymph node-targeting ability, demonstrating enhanced antigen-capturing capability. We loaded PABD-PGEA with doxorubicin (DOX), a drug known to induce immunogenic cell death (ICD) in tumor cells, to form DOX@PABD-PGEA nanomicelles. DOX@PABD-PGEA inhibited tumor growth and extended the survival of mice with B16F10 melanoma through chemotherapy and immunotherapy. Notably, DOX@PABD-PGEA prevented tumor recurrence post-surgery by promoting efficient antigen presentation and reversing immunosuppression in the tumor microenvironment. Our findings suggest that DOX@PABD-PGEA, as an antigen-capturing nanoparticle, provides a safe and effective platform for in situ cancer vaccines and improves cancer immunotherapy.