GSH‐Depleted Nanozymes with Hyperthermia‐Enhanced Dual Enzyme‐Mimic Activities for Tumor Nanocatalytic Therapy

TLDR

Nanocatalytic therapy using nanozymes is an emerging approach for malignant tumors, yet their catalytic activity in the tumor microenvironment remains insufficient. The study develops a PEG/Ce‑Bi@DMSN nanozyme and introduces photothermal therapy to enhance its dual enzyme‑mimicking activity and glutathione depletion for tumor treatment. The PEG/Ce‑Bi@DMSN nanozyme, composed of Bi₂S₃ nanorods coated with dendritic mesoporous silica and decorated with ceria, shows peroxidase‑ and catalase‑like activities in acidic tumor conditions, consumes glutathione, and its NIR‑II photothermal effect further boosts these catalytic functions. The combined hyperthermia and dual enzyme‑mimicking nanozyme treatment markedly increases ROS‑mediated therapeutic efficacy, demonstrating proof of concept for hyperthermia‑augmented nanozyme tumor ablation.

Abstract

Abstract Nanocatalytic therapy, using artificial nanoscale enzyme mimics (nanozymes), is an emerging technology for therapeutic treatment of various malignant tumors. However, the relatively deficient catalytic activity of nanozymes in the tumor microenvironment (TME) restrains their biomedical applications. Here, a versatile and bacteria‐like PEG/Ce‐Bi@DMSN nanozyme is developed by coating uniform Bi 2 S 3 nanorods (NRs) with dendritic mesoporous silica (Bi 2 S 3 @DMSN) and then decorating ultrasmall ceria nanozymes into the large mesopores of Bi 2 S 3 @DMSN. The nanozymes exhibit dual enzyme‐mimic catalytic activities (peroxidase‐mimic and catalase‐mimic) under acidic conditions that can regulate the TME, that is, simultaneously elevate oxidative stress and relieve hypoxia. In addition, the nanozymes can effectively consume the overexpressed glutathione (GSH) through redox reaction. Photothermal therapy (PTT) is introduced to synergistically improve the dual enzyme‐mimicking catalytic activities and depletion of the overexpressed GSH in the tumors by photonic hyperthermia. This is achieved by taking advantage of the desirable light absorbance in the second near‐infrared (NIR‐II) window of the PEG/Ce‐Bi@DMSN nanozymes. Subsequently the reactive oxygen species (ROS)‐mediated therapeutic efficiency is significantly improved. Therefore, this study provides a proof of concept of hyperthermia‐augmented multi‐enzymatic activities of nanozymes for tumor ablation.