Zheng Zou,1,* Xiaojun Bi,2,* Huan Ma,3 Ligang Chen,1 Hai Jin,1 Shun Gong,1 Xinning Li,1 Xiyu Liu1 

1Department of Neurosurgery, General Hospital of Northern Theater Command, Liaoning, 110016, People’s Republic of China; 2Department of Urology, General Hospital of Northern Theater Command, Liaoning, 110016, People’s Republic of China; 3The Fourth Affiliated Hospital, China Medical University, Liaoning, 110031, People’s Republic of China

*These authors contributed equally to this work

Correspondence: Xiyu Liu, Email lilsha0108@163.com

Abstract: Atherosclerosis (AS) is a complex, multifactorial cardiovascular disease characterized by lipid accumulation, chronic inflammation, oxidative stress, and endothelial dysfunction. Conventional therapies, including lipid-lowering and anti-inflammatory agents, offer limited efficacy due to inadequate lesion targeting, low bioavailability, and systemic side effects. Nanozymes, which engineered nanomaterials with intrinsic enzyme-mimetic catalytic activities have recently emerged as a transformative therapeutic strategy capable of simultaneously modulating oxidative stress, inflammation, and lipid metabolism. This review comprehensively summarizes recent advances in nanozyme-based interventions for AS, focusing on representative systems such as Prussian blue, cerium oxide, selenium-based, and multifunctional composite nanozymes. We critically discuss their design principles, catalytic mechanisms, lesion-targeting strategies, and therapeutic outcomes in preclinical models. Additionally, we highlight key translational challenges, including biosafety concerns, pharmacokinetic limitations, and manufacturing standardization, which currently impede clinical application. By integrating catalytic activity with targeted delivery and microenvironment-responsive functionalities, nanozymes offer a promising paradigm for precision therapy in AS. Future research should prioritize enhancing biocompatibility, optimizing therapeutic specificity, and establishing scalable, reproducible fabrication methods to facilitate clinical translation. This review aims to provide a systematic framework and insightful guidance for advancing nanozyme-based therapeutics toward clinical application in cardiovascular disease management.

Keywords: atherosclerosis, nanozymes, drug delivery, nanomedicine