Construction of In Situ Personalized Cancer Vaccines by Bioorthogonal Catalytic Microneedles for Augmented Melanoma Immunotherapy

nanosheets supported Pd into swellable microneedles, the bioorthogonal microneedles are constructed to catalyze the depropargylation reaction of doxorubicin (DOX) prodrug and imiquimod (IMQ) prodrug in situ. The activated DOX at subcutaneous tumor sites induced strong ICD and released tumor-associated antigens. Concurrently, the activated IMQ acts as a Toll-like receptor (TLR7) agonist, enhancing the anti-tumor immune response. In vivo experiments demonstrate that this immunotherapy achieves ≈97% inhibition of primary tumors and effectively inhibits untreated distant tumors (≈94% inhibition) and lung metastasis (≈92% inhibition).