Cardiovascular diseases (CVD) remain the leading causes of death and disability worldwide. The global burden is rising in part because of population ageing and increasing prevalence of risk factors such as diabetes, obesity, hypertension, and hyperlipidaemia. New medical and advanced therapies are urgently required to improve outcomes, but the full potential of many emerging treatments is limited by inadequate delivery to the heart. Effective, safe, and organ-specific delivery systems are therefore essential to translate molecular and cellular advances into clinical benefit for patients with CVD.
Current established delivery strategies for cardiac therapies include direct intramyocardial injection and catheter-based intracoronary delivery. While these methods can place therapeutics directly into or near myocardial tissue, they are invasive and necessitate specialized procedural infrastructure and expertise. The invasiveness of these approaches restricts their applicability across broader patient populations and clinical settings.
Intramyocardial injection delivers therapy directly into myocardial tissue, and catheter-based intracoronary delivery administers agents via the coronary circulation. Both provide localized dosing but require interventional procedures. The source review emphasizes that the invasiveness of these techniques limits clinical application despite their ability to concentrate therapeutic agents in the heart.
Cardiotropic adeno‑associated virus vectors represent a less invasive route to target therapeutics to the heart. Their tropism for cardiac tissue makes them attractive for gene delivery. However, the review notes key limitations—most notably immunogenicity—that complicate their clinical use. Immune responses to viral capsids and pre-existing neutralizing antibodies can reduce transduction efficiency and raise safety concerns. These immunological issues remain important translational barriers for AAV-mediated cardiac gene therapy.
Extracellular vesicles (EVs) have emerged as a promising biologically derived delivery platform. EVs can carry proteins, RNAs, and small molecules, and may be modified to improve targeting. The review includes EVs among the leading emerging approaches for delivering small molecules, biologics, nucleic acid therapeutics, and gene therapies to the heart. Specific performance metrics and comparative data were not reported in the abstract.
Microbubble-mediated delivery, often used with ultrasound, is another modality discussed as an emerging method to enhance cardiac delivery. Microbubbles permit localized payload release under ultrasound guidance, potentially improving myocardial delivery while limiting systemic exposure. Details on clinical translation status or efficacy were not provided in the source abstract.
Nanoparticle platforms are highlighted as versatile carriers capable of transporting a broad range of therapeutic modalities to cardiac tissue. Surface chemistry, size, and targeting ligands can be tuned to modify biodistribution. The review identifies nanoparticles as a promising strategy for targeted cardiac therapy, including delivery of small molecules, biologics, nucleic acids, and gene therapies.
Across all delivery systems, three interrelated challenges are emphasized: host immune responses (immunogenicity), unintended distribution to non-cardiac tissues (off-target effects), and suboptimal myocardial delivery efficiency. These limitations must be addressed to realize safe and effective clinical applications. The review underscores that overcoming these hurdles is a prerequisite to broad clinical translation.
The article discusses several technical strategies to improve cardiac specificity and therapeutic index. These include surface modifications of delivery vehicles, incorporation of cardiac‑homing peptides, membrane cloaking techniques to evade immune recognition, and organ‑targeting technologies that favor myocardial accumulation. Collectively, these methods aim to increase delivery efficiency to the heart while reducing systemic exposure and immune-mediated clearance.
The review frames cardiac-targeted delivery platforms as applicable to a range of cardiovascular indications. Specific therapeutic goals include treating ischaemic heart disease, heart failure, and cardiac arrhythmias. The platforms under discussion are intended to support delivery of diverse therapeutic classes: small molecules, biologics, nucleic acid therapeutics, and gene therapies. The abstract does not provide granular outcome data or comparative clinical trial results.
Emerging cardiac-targeting delivery systems—intracoronary and intramyocardial approaches, cardiotropic adeno-associated virus vectors, extracellular vesicles, microbubbles, and nanoparticles—offer promising routes to improve delivery of advanced therapies to the heart. However, addressing immunogenicity, off-target distribution, and limited delivery efficiency is essential before these technologies can deliver broad clinical benefit. Surface engineering, targeting ligands, membrane cloaking, and organ-targeting strategies are likely to play central roles in future development. The review emphasizes opportunities for these platforms to expand effective treatments for ischaemic heart disease, heart failure, and arrhythmias, while noting that translational challenges remain.
Note: The source abstract summarizes the state-of-the-art and strategic directions but does not report specific quantitative results, comparative efficacy metrics, or detailed clinical trial outcomes in the abstract text.