Perovskite immunoadjuvant: Remodeling the immunosuppressive microenvironment via photothermal catalysis to enhance T-cell recruitment and amplify the immune response.

Abstract

Immunotherapeutic efficacy is markedly compromised in "cold" tumors, largely as a consequence of the immunosuppressive milieu within the TME, characterized by hypoxia, a fortified antioxidant defense (e.g., elevated glutathione), and insufficient immunogenicity. This necessitates next-generation strategiy that can remodel the TME and trigger strong anti-tumor immunity. Herein, we engineered an intelligent photothermo-catalytic immunoadjuvant based on polyvinylpyrrolidone (PVP)-modified lanthanum manganite oxide perovskites (La_0.93MnO₃@PVP, LMOP), which synergizes with photothermal therapy (PTT) to amplify systemic anti-tumor immunity. LMOP demonstrated inherent catalytic activities mimicking both catalase (CAT) and glutathione peroxidase (GPx), which are markedly enhanced under PTT-induced hyperthermia, establishing a thermo-catalytic cascade. This synergy effectively remodeled the TME by generating O₂ to alleviate hypoxia and depleting glutathione to disrupt the antioxidant shield. The resulting oxidative stress, coupled with PTT, not only inflicted direct cytotoxicity but also induced mitochondrial damage, thereby triggering a potent immunogenic cell death (ICD) cascade. Remarkably, LMOP-mediated PTT effectively suppressed tumor growth, promoted dendritic cell (DC) maturation and extensive accumulation of CD4⁺ and CD8⁺ T cells. This immunoadjuvant design strategy presents a promising paradigm for converting immunosuppressive "cold" tumors into "hot," therapy-responsive phenotypes.