From barrier to guide: Exploiting disease-specific hemodynamics for enhanced nanodrug targeting in cardiovascular diseases

Cardiovascular diseases (CVDs) remain the leading cause of global mortality. Conventional systemic drug administration is plagued by issues such as suboptimal bioavailability and off-target effects. As an emerging vehicle, nanoparticles offer the potential to enhance therapeutic efficacy and reduce side effects through their targeted delivery properties. The hemodynamic characteristics under pathological conditions directly determine the success of targeted delivery by regulating the distribution, retention, and extravasation of nanoparticles within the circulation. This review systematically summarizes the pathological characteristics and disease-specific hemodynamic features of common CVDs: atherosclerosis, aneurysms, phlebitis, and venous thromboembolism. It thoroughly examines their critical influence on the delivery behavior of nanoparticles in blood and summarizes three targeted delivery strategies: passive targeting achieved by regulating nanocarrier properties, active targeting realized through the design of stimuli-responsive carriers, and homing effects attained via biomimetic modifications. Additionally, it summarizes relevant computational, experimental, and in vivo imaging methodologies for simulating blood flow dynamics and monitoring nanocarrier behavior. This review aims to provide a systematic perspective for understanding the role of hemodynamics in targeted delivery of nanomedicines, and to offer theoretical foundations and research paradigms for designing more efficient and lesion-selective cardiovascular nano-delivery systems.