Engineering extracellular vesicles for targeted therapeutics in cardiovascular disease

Abstract

Extracellular vesicles (EVs) are nanosized particles secreted by cells that play crucial roles in intercellular communication, especially in the context of cardiovascular diseases (CVDs). These vesicles carry complex cargo, including proteins, lipids, and nucleic acids, that reflects the physiological or pathological state of their cells of origin. Multiomics analysis of cell-derived EVs has provided valuable insights into the molecular mechanisms underlying CVDs by identifying specific proteins and EV-bound targets involved in disease progression. Recent studies have demonstrated that engineered EVs, which are designed to carry specific therapeutic molecules or modified to enhance their targeting capabilities, hold promise for treating CVDs. Analysis of the EV proteome has been instrumental in identifying key proteins that can be targeted or modulated within these engineered vesicles. For example, proteins involved in inflammation, thrombosis, and cardiac remodeling have been identified as potential therapeutic targets. Furthermore, the engineering of EVs to increase their delivery to specific tissues, such as the myocardium, or to modulate their immunogenicity and therapeutic efficacy is an emerging area of research. By leveraging the insights gained from multiomics analyses, researchers are developing EV-based therapies that can selectively target pathological processes in CVDs, offering a novel and potentially more effective treatment strategy. This review integrates the core findings from EV multiomics analysis in the context of CVDs and highlights the potential of engineered EVs in therapeutic applications.

Keywords: cardiovascular diseases (CVDs); engineering; extracellular vesicles (EVs); multiomics analysis; targeted therapeutics.

Figure 1

Composition and functional roles of EVs in CVDs. EVs, including proteins, lipids, nucleic acids and metabolites, have been identified as carriers of essential biomolecules that influence key biological processes, such as angiogenesis, inflammation regulation, cardiomyocyte survival and regeneration, and tissue repair. The figure was partly generated via Servier Medical Art, provided by Servier, licensed under a CC BY 3.0.

Figure 2

Engineering strategies for the targeting and functional modulation of EVs. Strategies such as genetic modification of parent (donor) cells to overexpress therapeutic nucleic acids or proteins, surface modification for improved targeting (e.g., cardiac-homing peptides), and cargo loading techniques (e.g., extrusion, freeze–thaw cycles, sonication, electroporation, incubation or combination with biomaterials) have been developed. These strategies aim to improve targeted delivery to cardiovascular tissues, functional modulation of EVs, and their ability to support angiogenesis, reduce fibrosis, and repair damaged heart tissue. The figure was partly generated via Servier Medical Art, provided by Servier, licensed under a CC BY 3.0.

Figure 3

Therapeutic applications and challenges of EV-based therapies for CVDs. The therapeutic applications of EVs include various CVDs, including myocardial infarction (MI), hypertension, atherosclerosis, and diabetic cardiomyopathy, where EVs promote tissue repair, reduce inflammation, and increase angiogenesis. On the diagnostic side, EVs show promise as biomarkers for CVDs, with their lipid, protein, and RNA contents in blood and body fluids providing critical information for early detection and disease monitoring. The challenges faced in the clinical translation of EV-based therapies include issues related to large-scale production, standardization of isolation and characterization techniques, the “batch effect” leading to variability in EVs properties, and concerns over the safety of EV-based treatments (e.g., off-target effects, immunogenicity of EVs and radioactivity of the tracer). These barriers must be overcome to fully realize the potential of EVs in CVDs theranostics. The figure was partly generated via Servier Medical Art, provided by Servier, licensed under a CC BY 3.0.