Advanced Cardiac-Targeting Delivery Systems Promise Enhanced Efficacy for Heart Disease Therapies

Cardiovascular diseases (CVD) are the leading causes of death and disability globally, with their burden rising due to aging populations and increasing risk factors like diabetes, obesity, hypertension, and hyperlipidaemia. Current advanced therapies for CVD often suffer from inadequate delivery to the heart. Established methods like intramyocardial injection and catheter-based intracoronary delivery are invasive, limiting clinical application. While cardiotropic adeno-associated virus (AAV) vectors offer less invasiveness, they pose challenges related to immunogenicity, highlighting an urgent need for more effective and safer cardiac-targeted delivery strategies.

This article provides a state-of-the-art review synthesizing recent advancements in cardiac-targeting delivery systems. It examines various emerging approaches, including local intracoronary catheter-based delivery, cardiotropic adeno-associated viruses, extracellular vesicles, microbubbles, and nanoparticle delivery platforms. The review also explores strategies employed to enhance targeting specificity and efficiency, such as surface modifications, the use of cardiac-homing peptides, membrane cloaking, and broader organ-targeting technologies, for delivering small molecules, biologics, and nucleic acid therapeutics.

The review highlights several promising cardiac-targeting delivery systems poised to improve outcomes in CVD. Cardiotropic adeno-associated virus vectors are discussed for their ability to target therapeutics to the heart, though their immunogenicity remains a key challenge. Emerging platforms like extracellular vesicles, microbubbles, and nanoparticle delivery systems are identified as versatile carriers for a range of advanced therapies. These systems leverage sophisticated strategies, including surface modifications, cardiac-homing peptides, and membrane cloaking, to achieve enhanced cardiac specificity.

These advanced delivery methods are designed to deliver a range of therapies, including small molecules, biologics, nucleic acid therapeutics, and gene therapies, directly to the heart, addressing conditions like ischaemic heart disease, heart failure, and cardiac arrhythmias. However, the review emphasizes that challenges concerning immunogenicity, off-target effects, and delivery efficiency must be overcome for these technologies to reach their full therapeutic potential.