Targeted nanoprobe for magnetic resonance imaging-guided enhanced antitumor via synergetic photothermal/immunotherapy

Synergistic photothermal/immunotherapy has garnered significant attention for its potential to enhance tumor therapeutic outcomes. However, the fabrication of an intelligent system with a simple composition that simultaneously exerts photothermal/immunotherapy effect and imaging guidance function still remains a challenge. Herein, a glutathione (GSH)-responsive theranostic nanoprobe, named HA-MnO₂/ICG, was elaborately constructed by loading photothermal agent (PTA) indocyanine green (ICG) onto the surface of hyaluronic acid (HA)-modified manganese dioxide nanosheets (HA-MnO₂) for magnetic resonance (MR) imaging-guided synergetic photothermal/immuno-enhanced therapy. In this strategy, HA-MnO₂ nanosheets were triggered by the endogenous GSH in tumor microenvironment to generate Mn²⁺ for MR imaging, where the longitudinal relaxation rate of HA-MnO₂/ICG was up to 14.97 mM^-1s^-1 (∼24 times than that found in a natural environment), demonstrating excellent intratumoral MR imaging. Moreover, the HA-MnO₂/ICG nanoprobe demonstrates remarkable photothermal therapy (PTT) efficacy, generating sufficient heat to induce immunogenic cell death (ICD) within tumor cells. Meanwhile the released Mn²⁺ ions from the nanosheets function as potent immune adjuvants, amplifying the immune response against cancer. In vivo experiments validated that HA-MnO₂/ICG-mediated PTT was highly effective in eradicating primary tumors, while simultaneously enhancing immunogenicity to prevent the growth of distal metastasis. This hybrid HA-MnO₂/ICG nanoprobe opened new avenues in the design of MR imaging-monitored PTT/immuno-enhanced synergistic therapy for advanced cancer.