Plaque‐Targeted Delivery of Fluoride‐Free MXene Nanozyme for Alleviating Atherosclerosis via Sonocatalytic Therapy

Abstract Atherosclerosis is an oxidative stress‐induced chronic inflammatory condition underpinning the progression of cardiovascular diseases (CVDs), ultimately resulting in leading mortality rate globally. Ultrasound (US)‐triggered catalysis offers localized treatment for deep‐seated plaques effectively and safely, with demand for targeted delivery and anti‐inflammatory properties of sonosensitizers. 2D MXene‐based nanomedicine is garnering attention because of their intriguing catalytic properties of scavenging excessive reactive oxygen species (ROS), yet MXene‐assisted sonocatalytic therapy (SCT) for treating CVDs remains scarce. Here, this study reports a dual enzyme‐mimicking and US‐responsive MXene termed Nb 2 C‐Pt@HA‐PEG for alleviating atherosclerosis. US irradiation enhances the capability of Nb 2 C‐Pt@HA‐PEG nanozymes in eliminating broad‐spectrum ROS and resolving vascular inflammation. Besides, actively targeting lesional macrophages improves their systemic delivery to plaque and further boosts anti‐atherosclerotic efficacy, contributing to ≈30% plaque size reduction and a more stabilized plaque phenotype. Notably, etching without hydrofluoric acid renders this nanozyme highly biocompatible. In long‐term biosafety studies, Nb 2 C‐Pt@HA‐PEG is pronouncedly cleared from major organs and no severe changes of liver and kidney functions are observed. Consequently, this work demonstrates that Nb 2 C‐Pt@HA‐PEG‐mediated SCT effectively ameliorates advanced atherosclerosis without inducing severe cytotoxicity, offering promising translational potential of MXene‐based nanomedicine. Besides, it broadens application prospects of MXenes to the biomedical field of treating CVDs.