Work

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

Year: 2025

Type: article

Abstract: 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.

Source: Advanced Science

DOI: 10.1002/advs.202512578