Engineered exosomes: a promising drug delivery platform with therapeutic potential

Abstract

Exosomes, small membranous vesicles naturally secreted by living cells, have garnered attention for their role in intercellular communication and therapeutic potential. Their low immunogenicity, high biocompatibility, and efficient biological barrier penetration make them promising drug delivery vehicles. This review spans research developments from 2010 to 2025, covering the engineering of exosomes to optimize cargo loading and targeting specificity. We discuss their applications in treating cardiovascular diseases, liver fibrosis, immune diseases, and neurological diseases, alongside ongoing clinical trials and industry progress. Future challenges include scalability, standardization, and minimizing off-target effects. We propose strategies to address these hurdles, such as bioengineering techniques and improved isolation methods. By synthesizing current knowledge and outlining future directions, this review aims to guide researchers toward harnessing exosomes for disease treatment.

Keywords: Exosomes; and nervous disorders; cardiovascular diseases; immune diseases; liver fibrosis.

FIGURE 1

The structure and formatting process of exosomes secreted from cells. In the beginning, exosomes form with the inward budding of the cytoplasmic membrane. Exosomes contain various molecules, including lipids, proteins, DNA, and RNA. These vesicles then turn into intraluminal vesicles (ILVs) as the early stage of exosomes and later develop into a late stage called multivesicular bodies (MVBs). Finally, the MVBs can be degraded inside the cells by lysosomes or autophagosomes. MVBs can directly fuse the plasma membrane where ILVs are released to the intercellular space between cells as exosomes to regulate the downstream signaling pathways.

FIGURE 2

Exosomes interact with target cells through multiple pathways, primarily in three ways. They can be internalized by target cells via endocytosis, after which they fuse with the endosome membrane to release their contents into the cytoplasm. Alternatively, exosomes may directly fuse with the target cell membrane. Additionally, exosomes can directly enter target cells through receptor-ligand interactions, where bioactive ligands on the exosome surface bind to specific receptors on the target cells, facilitating the delivery of their contents.

FIGURE 3

Schematic representation of exosome purification by differential ultracentrifugation. Culturing different types of cells and collecting culture medium, including apoptotic bodies, exosomes, and microvesicles. Exosomes are isolated by differential ultracentrifugation from low to high. The purified exosomes are characterized by size and morphology through TEM.

FIGURE 4

Exosomes derived from cardiac cells influence heart function through apoptosis regulation, fibrosis modulation, and angiogenesis support. Exosomes derived from different cell types in the heart, including cardiomyocytes, endothelial cells, vascular smooth muscle cells, cardiac fibroblasts, immune cells, and resident stem cells, can influence heart functions via the delivery of their cargos including nucleic acid, lipid, and protein. These cargos delivered by exosomes can reach all kinds of cells including cardiomyocytes, vascular smooth muscle cells, endothelial cells, cardiac fibroblasts and inflammatory cells and resident stem cells, in the heart via the bloodstream or directly through intracellular communication to employ their therapeutic benefits on apoptosis, fibrosis, and angiogenesis for myocardial recovery.

FIGURE 5

Exosomes contribute to the basic processes of innate and adaptive immunity. The immunoregulatory functions of exosomes mainly include affecting antigen presentation directly or indirectly to regulate the development of B cells and the activation of T cells including CD4T and CD8T cells, immunosuppression, the inflammatory response, and intercellular communication in different immune cells.

FIGURE 6

Exosomes contribute to liver fibrosis by targeting HSCs. Hepatocytes can be damaged due to many factors, including alcohol, lipids, and virus infection, specifically hepatitis virus (HBV/HCV). A variety of different pathways by different cells’ functions mediate chronic inflammation that exacerbates liver fibrosis. Immune cells including Kupffer cells, macrophages, and HSCs, secrete a lot of proinflammatory cytokines to promote the infiltration of inflammatory cells, and aggravate liver inflammation. As a result of liver injury, exosomes secreted by activated hepatocytes contain macromolecules that drive HSCs from quiescent HSCs to activated HSCs. Meanwhile, HSCactivation and proliferation directly drive extracellular matrix (ECM) deposition increases, resulting in liver fibrosis and liver dysfunction.

FIGURE 7

Exosomes as drug delivery vehicles and therapeutic targets for treating neurological disorders. During in vivo systems, exosomes can carry their own substances or therapeutic exogenous cargoes including DNA, RNAs, lipids, and proteins through the blood-brain barrier (BBB) into the damaged sites of the central nervous system (CNS), with low toxicity and immunogenicity. MSC: mesenchymal stem cells.