Cardiac-targeted delivery of advanced medical therapies for heart disease.

Cardiovascular diseases (CVD) are the leading causes of death and disability worldwide with their global burden on the rise due to the ageing population and escalating prevalence of CVD risk factors, such as diabetes, obesity, hypertension, and hyperlipidaemia. As such, new treatments are urgently needed to improve health outcomes in patients with CVD. However, the efficacy of emerging medical and advanced therapies for CVD may be hampered by their inadequate delivery to the heart. Established delivery strategies such as intramyocardial injection and catheter-based intracoronary delivery technologies require an invasive intervention, thereby limiting their clinical application. Although cardiotropic adeno-associated virus vectors, which target therapeutics to the heart are less invasive they have their own challenges in terms of immunogenicity. This article provides a state-of-the-art review of the recent advances in cardiac-targeting delivery systems including local intracoronary catheter-based delivery, cardiotropic adeno-associated viruses, extracellular vesicles, microbubbles, and nanoparticle delivery platforms, which have emerged as promising approaches for targeting the delivery of medical and advanced therapies such as small molecules, biologics, nucleic acid therapeutics, and gene therapies to the heart to combat CVD. However, challenges concerning immunogenicity, off-target effects, and delivery efficiency must be overcome to realize their therapeutic potential as safe and effective therapies. By leveraging surface modifications, cardiac-homing peptides, membrane cloaking, and organ-targeting technologies, the emerging cardiac-targeting delivery systems promise more effective medical and advanced therapies for a wide range of CVD, including ischaemic heart disease, heart failure, and cardiac arrhythmias.