# Beyond Catalytic Therapy: Copper‐Paeonol Nanozymes Disrupt Fascin‐Mediated Actin Bundling to Suppress Tumor Growth and Metastasis

## TL;DR

Copper-paeonol nanozymes disrupt actin bundling and generate reactive oxygen species to suppress tumor growth and metastasis.

## Contribution

A dual-functional nanozyme that targets fascin-mediated actin bundling and tumor-specific ROS generation is introduced.

## Key findings

- CuPaeNs disrupt fascin's actin-bundling activity, inhibiting tumor migration and invasion.
- CuPaeNs induce oxidative damage in cancer cells by converting H2O2 into hydroxyl radicals.
- CuPaeNs suppress melanoma glycolysis by blocking the fascin-YAP1-PFKFB3 signaling axis.

## Abstract

Fascin, an actin‐bundling protein universally upregulated in metastatic tumors, drives tumor migration and invasion by promoting filopodia and invadopodia formation, establishing it as a pivotal therapeutic target. Herein, copper‐paeonol nanozymes (CuPaeNs) is engineered through metal‐phenolic complexation, mimicking natural enzyme metal‐coordination microenvironments to confer peroxidase‐like activity. This enzymatic capability drives the conversion of tumor‐associated H2O2 into cytotoxic hydroxyl radicals, inducing oxidative damage in malignant cells. Notably, beyond inducing tumor catalytic therapy via targeted ROS generation, CuPaeNs directly disrupted the actin‐bundling activity of fascin, as evidenced by molecular docking, isothermal titration calorimetry, co‐immunoprecipitation, and immunofluorescence assays. Transcriptomic and biochemical analyses further revealed that CuPaeNs suppressed melanoma glycolysis by blocking the fascin‐YAP1‐PFKFB3 signaling axis. This study establishes metal‐phenolic nanozymes as a dual‐functional strategy that simultaneously triggers ROS overproduction to amplify tumor oxidative stress and disrupts fascin‐mediated metastasis, thereby modulating tumor metabolic reprogramming. This coordinated intervention establishes a novel treatment framework for malignancies characterized by fascin overexpression.

Copper‐paeonol nanozymes target tumor‐specific reactive oxygen species generation and disrupt fascin‐mediated actin bundling, effectively suppressing tumor growth and metastatic colonization.