Mild Photothermal Bimetallic Mesoporous Nanozyme Triggers Immunogenic Cell Death and Immune Contexture Remodeling for Precision Hepatocellular Carcinoma Treatment.

Treating hepatocellular carcinoma (HCC) remains a significant clinical challenge because of its immunosuppressive tumor microenvironment (TME) and poor response to immunotherapy. Immunogenic cell death (ICD) has emerged as a promising strategy for enhancing antitumor immunity through the release of tumor-associated antigens (TAAs) and damage-associated molecular patterns (DAMPs). However, efficient ICD induction requires precise regulation of oxidative stress, which is hindered by the robust antioxidant defenses of tumors, particularly glutathione (GSH)-mediated reactive oxygen species (ROS) scavenging. To address this, a platinum-cobalt (Pt/Co) bimetallic nanozyme (BNzyme) with a mesoporous structure is developed, which exhibited enzymatic activities similar to those of peroxidase (POD) and glutathione peroxidase (GPx). The Pt/Co BNzyme not only catalyzed H(2)O(2) to generate cytotoxic ROS but also simultaneously depleted GSH, amplifying oxidative stress and inducing tumor cell apoptosis. Additionally, near-infrared laser irradiation enhanced its enzymatic activity through mild photothermal effects, further promoting ICD. In vivo and in vitro experiments demonstrated that the Pt/Co BNzyme effectively remodeled the immune TME by increasing TAAs and dendritic-cell maturation. When combined with immune checkpoint inhibitors, this approach triggered robust systemic antitumor immunity and immune memory, effectively suppressing tumor growth and metastasis. The Pt/Co BNzyme exhibits excellent biosafety, offering a novel strategy for HCC immunotherapy.