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

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 Nb₂C-Pt@HA-PEG for alleviating atherosclerosis. US irradiation enhances the capability of Nb₂C-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, Nb₂C-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 Nb₂C-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.