Engineered manganese-BODIPY coordinated nanoadjuvants for enhanced NIR-II photo-metalloimmunotherapy

Immunotherapy, a pivotal and promising approach for tumor treatment, has demonstrated prominent clinical efficacy. However, its effectiveness is often impeded by insufficient antitumor immune responses attributed to the immunosuppressive tumor microenvironment (TME). The combination of immune activation through the stimulator of interferon genes (STING) pathway and phototherapy holds great potential for surmounting this challenge in advanced tumor immunotherapy. Herein, a novel manganese-boosted NIR-II photo-metalloimmunotherapy is proposed to synergistically enhance antitumour efficacy by fabricating Mn²⁺-BODIPY-based coordinated photo-immune nanoadjuvants (BMR), modified with tumor-targeted peptide cRGD. The obtained BMR could effectively deliver Mn²⁺ to tumor sites, and immunogenic cell death (ICD) was evoked by localized photothermal ablation of tumors using NIR-II laser irradiation. Simultaneously, pH-responsive release of Mn²⁺ would trigger the activation of STING pathway to promote the production of type I interferons (I-IFNs), significantly facilitating the maturation of dendritic cells (DCs) and polarization of macrophages to M1 phenotypes. Furthermore, by synergistically initiating systematic and robust antitumour immune responses, the BMR-mediated NIR-II photo-metalloimmunotherapy achieved remarkable therapeutic efficacy against both primary and lung metastasis of B16F10 tumors. Overall, in light of the versatile functionalities and synthetic flexibility of coordinated nanoadjuvants, formulated with photofunctional ligands and diverse metal ions, this work provides new insights into the design of metal coordination nanomedicine for effective antitumor photo-metalloimmunotherapy.