Aug 2026· Journal of Controlled Release· Vol 398, pp.
115255
· 0 citations· 197 references
Medicine
TL;DR
This review systematically analyzes the key issues facing EV-based therapeutic strategies in their progression from experimental research to clinical application, providing a practical theoretical framework for EV-based myocardial repair therapies and clarifying the prospects for EVs in the treatment of MI.
Abstract
Myocardial infarction (MI) remains a major challenge in clinical practice, as the irreversible loss of cardiomyocytes and the limited repair capacity of the adult heart constrain cardiac repair. Traditional cell therapy once held great promise, but its clinical application has been constrained by issues such as low cell survival, immune rejection and procedural complexity. Against this background, extracellular vesicles (EVs) have attracted attention as a paracrine delivery strategy. By delivering bioactive cargo, including proteins, nucleic acids and lipids, EVs mediate intercellular communication and thereby support cardiac repair. This review focuses on the clinical potential of EVs, comparing the advantages, limitations and safety risks of EVs from different cellular origins, and places particular emphasis on engineered delivery strategies aimed at improving targeting, retention and therapeutic efficacy. In parallel, we examine the core barriers to clinical translation, including large scale manufacturing challenges, batch to batch consistency, storage stability, and regulatory and ethical issues; it is these barriers, rather than insufficient efficacy, that constitute the key bottleneck to the clinical application of EVs. Compared with existing reviews, this review, by emphasizing a clinical translation perspective, systematically analyzes the key issues facing EV-based therapeutic strategies in their progression from experimental research to clinical application, providing a practical theoretical framework for EV-based myocardial repair therapies and clarifying the prospects for EVs in the treatment of MI.
Heart failure (HF), the terminal stage of most cardiovascular diseases, remains a major global health burden with limited therapeutic options that do not fully achieve myocardial repair or functional recovery. Extracellular vesicles (EVs), nanoscale membrane-bound particles released by cells, have been increasingly recognized as important mediators in the pathophysiology of HF and as potential therapeutic targets. As intercellular messengers carrying bioactive molecules, including proteins, lipids, and non-coding RNAs, EVs regulate gene expression and functional states in recipient cells. This review summarizes current evidence on the roles of EVs in key pathological processes of HF, including inflammation, mitochondrial dysfunction, myocardial hypertrophy, fibrosis, apoptosis, and angiogenesis. We also discuss their potential as circulating biomarkers for the diagnosis and prognosis of HF. In addition, we describe emerging therapeutic strategies, including stem cell-derived EVs and engineered EVs as delivery platforms for therapeutic molecules. Furthermore, we discuss the pharmacological implications of EVs in current heart failure treatment paradigms, highlighting their potential role in bridging mechanistic insights with clinical therapeutic strategies. Collectively, these findings highlight the relevance of EVs in HF research and suggest directions for future investigation.
Tingting Li, Jin Yang, Xinyue Ding et al.· Frontiers in Pharmacology· 0 citations
Cardiovascular disease remains the leading cause of death globally. In particular, ischemic heart disease represents the most common condition in clinics. Adult hearts have minimal regenerative capacity. Upon myocardial infarction, the formation of activated myofibroblasts replaces the massive loss of cardiomyocytes. Nanomedicine has emerged as a promising strategy for cardiovascular disease treatment, with synthetic nanoparticles and extracellular vesicles serving as representative delivery platforms. However, directly applying these nanomedicines faces several challenges, including insufficient cardiac targeting, poor retention rate at the injured site, and potential biocompatibility concerns. To overcome these limitations, different bioengineering approaches have been adopted. In this review, we discussed the landscape of cardiovascular nanomedicine, encompassing both synthetic nanocarriers and biological carriers and targeted delivery. We further evaluated the engineering approaches to enhance carrier performance. Multiple administration routes are also compared. Collectively, these advances represent a shift toward an integrated, multifunctional delivery platform with the potential to translate cardiac nanomedicine from bench to bedside.
Myocardial infarction (MI) remains a leading cause of heart failure. Although contemporary interventions improve early survival, they fail to promote cardiac repair or prevent long-term adverse remodeling. Microspheres, with injectability, high surface-to-volume ratio, and tunable structure, have emerged as versatile therapeutic platforms and have been clinically applied in chemotherapy, hemostasis, and long-acting injectable formulations. In MI therapy, microspheres can encapsulate diverse bioactive agents, modulate the infarct microenvironment in a minimally invasive manner, and promote cardiac repair. This review introduces microsphere morphology, size, materials, and major fabrication techniques, including emulsion-solvent evaporation, spray drying, electrospraying, and microfluidics. It also summarizes preclinical evidence on delivery routes, intramyocardial, epicardial, and intracoronary, and emphasizes design strategies. Furthermore, the use of microspheres for bioactive-agent delivery, cell therapy, and three-dimensional engineered cardiac tissues is reviewed. Finally, the limitations and future perspectives of microsphere-based therapy for MI are discussed, aiming to inspire innovative strategies and accelerate clinical translation.
Tailuo Liu, Ying Hao, Lifan Xu et al.· International journal of pha...· 0 citations
Simple Summary Cardiovascular diseases are the leading cause of death worldwide, accounting for 19.2 million deaths in 2023. When a heart attack occurs, the affected cardiomyocytes die rapidly, and the adult heart replaces them at only about 1% per year, far too slowly to compensate for the loss following a large infarction. Current treatments stabilise patients but cannot rebuild lost muscle. Over the past two decades, clinical trials have tested stem cells from bone marrow, fat tissue, umbilical cord blood, and reprogrammed adult cells. These approaches are consistently safe. Some have produced modest improvements in cardiac function and scar reduction, but the transplanted cells rarely persist long enough to form new heart muscle. The benefit they confer appears to arise mainly from signalling particles they release called extracellular vesicles and exosomes, which carry microRNAs and proteins that reduce scarring, stimulate blood vessel growth, and dampen post-injury inflammation. This finding has opened a new research direction: engineering those particles directly, without transplanting cells at all. This review examines the full range of cell-based strategies studied to date, the clinical trial evidence, the barriers to progress, and what engineered vesicles, bioengineered tissue constructs, gene editing, and improved trial design might offer.
