Nanocatalytic Tumor Therapy by Biomimetic Dual Inorganic Nanozyme‐Catalyzed Cascade Reaction

TLDR

Emerging nanocatalytic tumor therapies employ nontoxic inorganic nanoparticles to generate reactive oxygen species, and while nanozymes with enzyme‑like activity have been widely used for detection, few studies have explored their application in tumor therapy. This study constructs a biomimetic dual inorganic nanozyme platform that triggers cascade reactions for tumor‑microenvironment‑responsive nanocatalytic therapy. The platform co‑loads ultrasmall Au and Fe₃O₄ nanoparticles into dendritic mesoporous silica; Au acts as a glucose‑oxidase mimic to produce H₂O₂, which Fe₃O₄ peroxidase‑mimic then converts to hydroxyl radicals via a Fenton reaction. In vitro and in vivo evaluations demonstrate high therapeutic efficacy with a 69.08 % tumor‑suppression rate, confirming the composite nanocatalysts’ excellent biosafety and effectiveness.

Abstract

Abstract Emerging nanocatalytic tumor therapies based on nontoxic but catalytically active inorganic nanoparticles (NPs) for intratumoral production of high‐toxic reactive oxygen species have inspired great research interest in the scientific community. Nanozymes exhibiting natural enzyme‐mimicking catalytic activities have been extensively explored in biomedicine, mostly in biomolecular detection, yet much fewer researches are available on specific nanocatalytic tumor therapy. This study reports on the construction of an efficient biomimetic dual inorganic nanozyme‐based nanoplatform, which triggers cascade catalytic reactions for tumor microenvironment responsive nanocatalytic tumor therapy based on ultrasmall Au and Fe 3 O 4 NPs coloaded dendritic mesoporous silica NPs. Au NPs as the unique glucose oxidase‐mimic nanozyme specifically catalyze β‐D‐glucose oxidation into gluconic acid and H 2 O 2 , while the as produced H 2 O 2 is subsequently catalyzed by the peroxidase‐mimic Fe 3 O 4 NPs to liberate high‐toxic hydroxyl radicals for inducing tumor‐cell death by the typical Fenton‐based catalytic reaction. Extensive in vitro and in vivo evaluations have demonstrated high nanocatalytic‐therapeutic efficacy with a desirable tumor‐suppression rate (69.08%) based on these biocompatible composite nanocatalysts. Therefore, this work paves a way for nanocatalytic tumor therapy by rationally designing inorganic nanozymes with multienzymatic activities for achieving high therapeutic efficacy and excellent biosafety simultaneously.