# Biomimetic nanoplatform with multienzyme cascade activity boosting ROS generation and immune activation feedback for tumor therapy

## TL;DR

A new biomimetic nanoplatform boosts tumor treatment by combining ROS generation and immune activation through a cascade of enzyme-like activities.

## Contribution

The first reported glutathione oxidase- and L-cysteine oxidase-like activities of nano-realgar in tumor therapy.

## Key findings

- The nanoplatform's cascade catalytic effect enhances tumor suppression through ROS generation.
- ROS and immune activation create a positive feedback loop improving treatment outcomes.

## Abstract

Nanocatalytic medicine has emerged as a promising strategy for tumor therapy, utilizing nanozymes to generate cytotoxic reactive oxygen species (ROS). Despite significant progress, challenges persist, including low catalytic efficiency and inadequate tumor targeting. Herein, we report a tumor cell membrane coated biomimetic nanozyme platform (CMNP) containing manganese dioxide nanoparticles (MnO2@BSA), nano-realgar (NR), and doxorubicin (DOX). This nanoplatform targets tumors via biomimetic properties. In the tumor, MnO2 alleviates hypoxia by catalytically decomposing H2O2 to produce O2, thereby enhancing the enzymatic activity of NR. As the nanocrystalline form of a traditional Chinese medicine, NR exhibits glutathione oxidase (GSHOx)- and L-cysteine oxidase (LCO)-like activities, generating substantial cytotoxic ROS. These cascade catalysis-enhanced ROS not only induce tumor cell apoptosis but also activate immune responses in the tumor microenvironment. Furthermore, released DOX and Mn2+ ions recruit tumor-killing immune cells by inducing the immunogenic cell death (ICD) of tumor cells and activating the cyclic GMP-AMP synthase-stimulator of interferon genes (cGAS-STING) pathway, respectively. The tumor suppression stems from a positive feedback regulation driven by ROS generation and immune activation. Our study proposes a versatile nanoplatform that offers a two-pronged treatment strategy.

We report a biomimetic nanozyme platform (CMNP) containing manganese dioxide nanoparticles (MnO2@BSA), nano-realgar (NR), and doxorubicin (DOX) coated with tumor cell membrane. The tumor suppressive effects with CMNP treatment are amplified via synergism between the nanocatalytic cascade effect and the two-pronged treatment strategy. CMNP offers a novel and valuable approach for treating tumor.Image 1

•The Glutathione oxidase- and L-cysteine oxidase-like activities of nano realgar are first reported.•The cascade catalytic effect of multiple nanoenzymes promotes tumor treatment.•The positive feedback regulation of ‘oxidative stress-ferroptosis-immune activation’.

The Glutathione oxidase- and L-cysteine oxidase-like activities of nano realgar are first reported.

The cascade catalytic effect of multiple nanoenzymes promotes tumor treatment.

The positive feedback regulation of ‘oxidative stress-ferroptosis-immune activation’.