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Review
. 2021 Jan 1;11(5):2263-2277.
doi: 10.7150/thno.51571. eCollection 2021.

Targeted delivery of extracellular vesicles in heart injury

Peier Chen  1   2   3 , Ling Wang  4 , Xianglin Fan  1   2   3 , Xiaodong Ning  1   2   3 , Bin Yu  1   2   3 , Caiwen Ou  1   2   3 , Minsheng Chen  1   2   3
Affiliations
Review

Targeted delivery of extracellular vesicles in heart injury

Peier Chen et al. Theranostics. .

Abstract

Extracellular vesicles (EVs) are nanoscale extracellular vesicles derived from endocytosis that are crucial to intercellular communication. EVs possess natural biocompatibility and stability that allow them to cross biological membranes and that protect them from degradation. Recent studies have shown that EVs-mediated crosstalk between different cell types in the heart could play important roles in the maintenance of cardiac homeostasis and the pathogenesis of heart diseases. In particular, EVs secreted by different types of stem cells exhibit cardioprotective effects. However, numerous studies have shown that intravenously injected EVs are quickly cleared by macrophages of the mononuclear phagocyte system (MPS) and preferentially accumulate in MPS organs such as the liver, spleen, and lung. In this review, we discuss exosome biogenesis, the role of EVs in heart diseases, and challenges in delivering EVs to the heart. Furthermore, we extensively discuss the targeted delivery of EVs for treating ischemic heart disease. These understandings will aid in the development of effective treatment strategies for heart diseases.

Keywords: Biogenesis; Challenges; Extracellular Vesicles; Heart Injury; Targeted Delivery.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interest exists.

Figures

Figure 1
Figure 1
Intracellular biogenesis and secretion of extracellular vesicles. A: The process of exosome formation begins with early-sorting endosomes (ESE) formed by endocytosis on the surface of plasma membranes. Subsequently, ESE matures to generate a late endosome (LSE)/multivesicular body (MVB) and exosomes are released into the extracellular space by fusion of MVBs. B: Exosomes interact with target cells via receptors, fusion with plasma membrane, endocytosis, or release of their cargo.
Figure 2
Figure 2
Roles of extracellular vesicles in heart diseases. EVs play an important role in the maintenance of cardiac homeostasis and the pathogenesis of heart diseases. A: The role of EVs in pathophysiological processes. B: EVs as diagnostic biomarkers in heart diseases. C: EVs as therapeutic agents in heart diseases.
Figure 3
Figure 3
Overview of extracellular vesicles, their composition, isolation, and analysis in vivo. A: The composition of exosomes (including proteins, lipids, and nucleic acids). B: Exosomal isolation and purification techniques. C: Drug-loading techniques to produce EVs-based nanotherapeutics. D: Administration routes in EVs-based nanotherapeutics. E: Injection dose and frequency in EVs-based nanotherapeutics.
Figure 4
Figure 4
Macrophages eliminate circulating extracellular vesicles. Injected EVs are quickly cleared by macrophages of the mononuclear phagocyte system (MPS) and preferentially accumulate in MPS organs (e.g., liver, spleen, lung).
Figure 5
Figure 5
Targeted therapeutic delivery of extracellular vesicles in heart diseases. Three strategies for targeted delivery of therapeutic EVs to the heart. A: Encapsulation of EVs in hydrogels. B: Genetic engineering of EVs. C: Two-step EVs delivery.
See this image and copyright information in PMC

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