Recent Advances in Targeted and Microenvironment-Responsive Drug Delivery Nanoplatforms for Atherosclerosis Therapy

Atherosclerosis (AS), the primary driver of cardiovascular morbidity and mortality, frequently manifests as life-threatening clinical events triggered by the rupture of vulnerable plaques. Therefore, targeting the early mechanisms of plaque development is crucial to limit plaque progression and promote stability. However, current pharmacological interventions are often hampered by dose-limiting toxicity, non-specific distribution, and low bioavailability, limiting effective plaque regression. To address these challenges, intelligent nanoplatforms have emerged as a promising strategy to enable lesion-specific targeting and controlled drug release. This review systematically outlines active targeting strategies to achieve specific drug enrichment at atherosclerotic plaque by receptor-ligand interaction or biomimetic membrane functionalization. We further explore microenvironment-responsive therapeutic strategies to trigger on-demand drug release by exploiting the pathological hallmarks of plaques, such as acidic pH, elevated reactive oxygen species (ROS), or specific enzyme overexpression. Finally, the synergistic nanoplatforms that integrate active targeting with multimodal responsiveness are discussed. This review provides a theoretical framework and design principles for developing high-performance nanomedicines for the precise treatment of AS. • Recent advances in targeted and microenvironment-responsive nanoplatforms for precise atherosclerosis therapy are reviewed. • Targeted nanoplatforms significantly enhance drug enrichment within atherosclerotic plaques. • Microenvironment-responsive nanoplatforms enable responsive drug release. • Integrated nanoplatforms combining targeting, responsiveness, and combination therapies represent the future trend.