Nanotherapies for Atherosclerosis: Targeting, Catalysis, and Energy Transduction.

Abstract

Atherosclerosis (AS), the pathological cornerstone of global cardiovascular mortality, remains inadequately managed by current therapies due to low bioavailability, off-target effects, and inability to overcome plaque spatial heterogeneity. Nanotechnology solves these limitations through innovative designs that leverage its unique advantages: precise targeting, enhanced pharmacokinetic profile, and intrinsic functionalities. This review systematically examines three core therapeutic strategies: (1) Advanced target-engineered nanocarriers achieving lesion-specific precision via ligand modification, biomimetic camouflage, stimuli-responsive activation, and nanomotor propulsion; (2) Catalytic nanozymes reprogramming plaque microenvironments through intrinsic ROS scavenging and lipid metabolism modulation; (3) Energy-transducing nanoplatforms enabling physical intervention via photo-, sono-, and magnetic therapies. For each seminal study, we critically analyze the design rationale and innovations, elucidate underlying mechanisms, and demonstrate quantitative efficacy. Finally, we discuss the challenges and future directions for nanotherapeutics in AS management. This work provides the first comprehensive integration of material innovation and therapeutic advancement, charting a clinical translation pathway for AS nanomedicine.