Abstract
The global aging population has increased the burden of cardiovascular and cerebrovascular diseases, which remain leading causes of morbidity and mortality worldwide. In their pathogenesis, platelets not only promote thrombus formation but also exert proinflammatory effects that cause extensive inflammatory responses, accelerating atherosclerosis and endothelial dysfunction. Traditional systemic anti-platelet agents face considerable challenges in elderly patients due to the delicate balance between antithrombotic efficacy and bleeding risk. Polymeric anti-platelet carriers alter the risk-benefit balance between antithrombotic efficacy and bleeding complications through local, biomarker-guided drug delivery. This review systematically summarizes platelet dysfunction in age-related cardiovascular and cerebrovascular diseases and corresponding strategies for constructing precision-targeted polymeric carriers. We first summarize major platelet-related biomarkers that have emerged as actionable targets, including glycoprotein VI (GPVI), platelet-derived growth factor-B (PDGF-B) and its receptor PDGFR-β, reactive oxygen species (ROS), and disease-associated shear stress. We then review recent advances in surface engineering approaches for targeted delivery, with emphasis on ligand-guided targeting, biomimetic cloaking, and multivalent binding designs. Next, we discuss carrier architectures tailored to improve drug loading and enable controlled release, highlighting stimuli-responsive platforms that exploit thrombotic microenvironmental signals, such as acidic pH, enzyme enrichment, oxidative stress, and shear forces, to trigger site-specific drug liberation. We also outline synergistic strategies that integrate anti-inflammatory and thrombolytic actions with biomimetic features to more effectively manage cardiovascular and cerebrovascular disorders. Finally, we consider future opportunities for polymeric anti-platelet delivery systems, focusing on materials innovation, patient stratification and personalization, and translational considerations that will shape long-term clinical utility. Overall, this review underscores the promise of polymer-based anti-platelet carriers for the prevention and treatment of age-related cardiovascular and cerebrovascular diseases.