Immunotherapy has demonstrated the potential to cure melanoma, while the current response rate is still unsatisfactory in clinics. Extensive evidence indicates the correlation between the efficacy and pre-existing T-cell in tumors, whereas the baseline T-cell infiltration is lacking in low-response melanoma patients. Herein, we demonstrated the critical contribution of dendritic cells (DCs) on melanoma survival and baseline T-cell level, as well as the efficacy of immunotherapy. Capitalized on this fact, we developed a photothermal nano-vaccine to simultaneously promote tumor antigens presentation and DCs infiltration for enhanced immunotherapy. The nano-vaccine was composed of polyserotonin (PST) core and tannic acid (TA)/Mn2+ coordination-based metal-organic-framework (MOF) shell for β-catenin silencing DNAzyme loading, which was further integrated into dissolving microneedles to allow noninvasive and transdermal administration at melanoma skin. The nano-vaccine could rapidly penetrate skin upon microneedles insertion and exert a synergistically amplified photothermal effect to induce immunogenic cell death (ICD). The MOF shell then dissociated and released Mn2+ as a cofactor to self-activate DNAzyme for β-catenin suppression, which in turn caused a persistent CCL4 excretion to promote the infiltration of DCs into the tumor. Meanwhile, the liberated PST core could effectively capture and facilitate tumor antigens presentation to DCs. As a result, potent antitumor efficacies were achieved for both primary and distal tumors without any extra treatment, indicating the great promise of such a nano-vaccine for on-demand personalized immunotherapy of melanoma.

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