Abstract
Cardiovascular disease remains a major cause of morbidity and mortality worldwide, with myocardial infarction and pressure overload driving progressive cardiac injury and maladaptive remodeling that involve dynamic changes in vasculature, cells, and extracellular matrix. Current therapies do not fully prevent this process, creating a need for targeted interventions that can image and treat distinct pathogenic phases. This Review examines nanocarrier strategies for imaging and therapy across ischemic injury, inflammatory repair, fibrosis, and pressure-overload remodeling. Imaging systems exploit regional retention, phagocyte uptake, biochemical activation, or binding to extracellular matrix and fibroblast-associated targets. Preclinical therapeutic platforms deliver RNA, small molecules, or active materials to injured cardiomyocytes, inflammatory phagocytes, and activated fibroblasts. Administration route and timing influence cardiac cell targeting, though interventions acting on circulating cells, immune reservoirs, or extracardiac depots can benefit the heart without preferential myocardial accumulation. Human translation remains limited; fibroblast activation protein inhibitor tracers offer a clinical benchmark for mapping remodeling. We use "phase matching" to align route, target, payload, and functional assessment with a specific disease window and clinical decision. Progress depends less on maximal cardiac accumulation than on quantitative pharmacology, immune safety, reproducible manufacture, and added clinical value.