Precisely Delivered Mn 2+ Enables Efficiently Chemodynamic and Immunotherapy of Melanoma via a Multipoint Implanted Strategy

Tumor immunotherapy harnesses the host immune system to combat tumors, offering curative potential. However, their clinical efficacy is often limited by insufficient antitumor immune responses. Herein, we developed a degradable “multipoint implant” microneedle array (MI) that precisely delivers polydopamine (PDA)-coated manganese oxide nanocomposites (MDA) into tumors for simultaneous multisite release. Combined with PD-L1 antibodies, it was used for systemic immune modulation. The strategy exerts dual mechanisms: on the one hand, Mn 2+ released from flower-shaped MDA in the acidic tumor microenvironment activates the cGAS-STING pathway, synergizing with immune checkpoint inhibition (ICI) to regulate antigen presentation by dendritic cells and enhance T-cell responses in the cancer immune cycle; on the other hand, by precisely regulating the ratio of PDA to oxidized manganese in MDA, differentiated photothermal effects are generated under 808 nm laser irradiation, controlling its decomposition kinetics to achieve highly synergistic photothermal and chemotherapeutic effects. In vivo experiments demonstrate that this synergistic approach significantly enhances antitumor immune responses while inhibiting tumor growth, recurrence, and metastasis. The study provides a multipathway synergistic combination therapy strategy for enhancing antitumor immunotherapy.