Rare-Earth Nanomaterials for Advanced Theranostics of Atherosclerosis

Atherosclerosis (AS) poses major challenges for precise diagnosis and targeted therapy due to its complex inflammatory and oxidative plaque microenvironment. This review begins by dissecting the cellular and molecular hallmarks of AS progression, from endothelial dysfunction to plaque rupture, identifying key targets including adhesion molecules, scavenger receptors, and immune costimulatory pathways that can be exploited for nanotheranostic intervention. Rare-earth nanoparticles (RENPs) offer a versatile platform that integrates multimodal imaging with therapeutic functions. We highlight the strategic design of RENPs, including core-shell engineering, surface functionalization, and doping strategies, to enhance NIR-II luminescence, lifetime multiplexing, and X-ray-activated persistent luminescence for high-resolution vascular imaging and fluorescence-guided surgery. Their intrinsic enzyme-mimetic activities, particularly the cerium-based nanozymes that scavenge reactive oxidative species, are examined as a key therapeutic mechanism targeting oxidative stress within plaques. A critical discussion of biocompatibility analyzes the element- and form-dependent toxicity profiles, emphasizing the divergent effects between therapeutic nanomaterials and potentially harmful rare-earth ions. These insights underscore the necessity of rigorous safety evaluations alongside functional development. Finally, we outline future directions and challenges in the clinical translation of RENP-based theranostic strategies, emphasizing the need for optimized targeting, biosafety, and multifunctional integration to achieve the precise diagnosis and effective treatment of atherosclerotic cardiovascular diseases.