Synergistic Enhancement of Immunogenic Cell Death Through Photothermal/Photodynamic Effects via Complex Nanoenzymes for Pancreatic Cancer Therapy.

Abstract

Recent studies have revealed that the immunosuppression tumor mircroenvironment significantly impaired the efficacy of therapies against pancreatic cancer. Although photodynamic therapy (PDT)-induced immunogenic cell death (ICD) offers a promising approach to stimulate the immune response, its effectiveness is considerably constrained by tumor hypoxia. In this work, we proposed an innovative nanozyme system based on dendritic mesoporous silica nanoparticles, co-loaded with the photosensitizer IR808, MnO₂, and Pt nanozymes, to amplify ICD through synergistic catalytic activities. Upon tumor accumulation, the released MnO₂ and Pt nanozymes simultaneously catalyze the decomposition of H₂O₂ via their peroxidase- and catalase-like activities, generating cytotoxic ·OH while alleviating hypoxia to enhance IR808-mediated PDT. Under 808 nm laser irradiation, the system demonstrates combined photothermal and augmented photodynamic effects, leading to potent tumor ablation and robust ICD induction. Comprehensive evaluations revealed that this nanozyme system not only exhibits remarkable tumor suppression through multimodal therapy but also effectively activates systemic antitumor immunity both in vitro and in vivo. Furthermore, the platform enables precise cancer diagnosis through dual-modality magnetic resonance and near-infrared imaging capabilities. This study presents a novel paradigm for enhancing ICD and establishes a versatile theranostic strategy for pancreatic cancer treatment.