Endogenous and exogenous stimuli-responsive nanoparticles in the diagnosis and treatment for atherosclerosis

Atherosclerosis (AS), a chronic inflammatory disease characterized by lipid deposition in the arterial wall, serves as the primary pathological basis for cardiovascular diseases that contribute significantly to global morbidity and mortality. Recent advances in nanotechnology have enabled the design of smart nanoparticles for theranostic applications in AS. In particular, stimuli-responsive nanoparticles that react to endogenous cues, such as reactive oxygen species, pH, lipid, and enzymes within the AS microenvironment, have demonstrated considerable promise for targeted diagnosis and therapy. Likewise, nanoparticles engineered to respond to external stimuli, including ultrasound, light, and temperature, offer additional avenues for precise AS theranostics. These intelligent nanoparticles allow for targeted accumulation and controlled drug release specifically at atherosclerotic sites, thereby enhancing drug-loading capacity and delivery precision while reducing off-target effects and systemic toxicity. This review systematically outlines the research progress made over the past decade in the development of stimuli-responsive nanoparticles for AS theranostics, with special emphasis on their stimulus-triggered disassembly and degradation mechanisms. Finally, we provide an overview of the challenges and opportunities of applying these smart stimuli-responsive nanoparticles.