Plant-derived extracellular vesicles as emerging cardioprotective agents for cardiovascular diseases.

Abstract

Cardiovascular diseases (CVDs) remain a leading cause of global morbidity and mortality. Their complex and multifactorial pathogenesis, involving endothelial dysfunction, chronic inflammation, oxidative stress, metabolic dysregulation, and pathological remodeling, limits the long-term effectiveness of current therapeutic strategies and underscores the need for novel treatment approaches. Plant-derived extracellular vesicles (PDEVs) have recently emerged as promising cardioprotective agents because of their favorable biocompatibility, relatively low immunogenicity, abundant endogenous bioactive cargoes, and engineering flexibility. Owing to these properties, PDEVs possess dual characteristics as natural nanocarriers and bioactive therapeutic agents. Preclinical evidence from various in vitro and in vivo cardiovascular disease models indicates that PDEVs exert antioxidative, anti-inflammatory, immunomodulatory, and tissue-reparative effects, thereby attenuating myocardial injury, reducing oxidative stress, and promoting cardiomyocyte survival. Beyond their intrinsic therapeutic activities, PDEVs can also serve as multifunctional drug delivery vehicles for small-molecule drugs, nucleic acids, proteins, and natural bioactive compounds, improving cargo stability, bioavailability, and therapeutic performance. Recent advances in surface functionalization, membrane fusion, and biomimetic design have further enhanced their targeting capacity and functional controllability. This review focuses on the application of PDEVs in cardiovascular disease therapy, systematically summarizing their preparation, characterization, quality evaluation, and relative advantages and limitations compared with conventional nanocarriers. It further highlights their therapeutic effects in different cardiovascular disease models, drug delivery applications, engineering strategies, and the current progress and key challenges in clinical translation. Continued advances in this field may promote the translation of PDEVs from experimental research to clinical application and broaden their value in cardiovascular nanomedicine.