Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes


Intercellular communication is absolutely essential to cell development and the maintenance of homeostasis in multicellular organisms. These communications between cells can be localized or distant. Local communication involves direct contact between cells facilitated through communication systems, like a gap junction that connects the cytoplasm of cells adjacent to one another, allowing signaling substances to pass between the cells. On the other hand, distant intercellular communication is facilitated by molecules like hormones that send signals through circulatory system to other parts of the body. Another case of distant intercellular communication also occurs in extracellular vesicle (EV), which is a membrane-based structure. These EVs serve as vehicles to carry different types of cellular cargo—such as lipids, proteins, receptors and effector molecules—to the recipient cells.

There are three types of EVs that are differentiated based on their intracellular origins: apoptotic bodies, microvesicles and exosomes. Apoptotic bodies have a size ranging from 50 to 5000 nm and contain cellular contents such as deoxyribonucleic acid (DNA), ribonucleic acid (RNA) and histone proteins. Microvesicles are formed through the outward budding and fission from plasma membranes, with a size ranging from 50 nm to 1000 nm. The final category of EVs is exosomes, which differ from microvesicles mainly in terms of their intracellular origin and size.

Over the past decades, there has been extensive research carried out on exosomes. While working with maturing reticulocytes, researchers first observed the formation of “an intracellular sac filled with small membrane-enclosed structure of nearly uniform size”. These formed intracellular vesicles and released contents outside the cell, as opposed to inside of cell (endocytosis), where external molecules are internalized into the membrane-bound structure. Hence, these intracellular-formed vesicles were named “exosome”.

Exosomes are originated from endosomes with a smaller size, ranging from 40 to 100 nm. They are secreted by all cell types and can be found in most body fluids, including blood, saliva, and urine. An exosome is a “nanosphere” with a bilayerd membrane, containing various types of lipids and proteins derived from the parent cell. Some of these proteins include transport proteins, heat shock proteins, proteins associated with multi-vesicular body biogenesis (MVB), and tetraspanin. In addition to proteins, exosomes are comprised of different types of lipids, such as cholesterol, sphingolipids, phosphoglycerides, ceramides, and saturated fatty acid chains. The composition of exosomes is critical since they serve as a biomarker and provide an indication of its function in biological processes.

Ha D, Yang N, Nadithe V. (2016) Exosomes as therapeutic drug carriers and delivery vehicles across biological membranes: current perspectives and future challenges. Acta Pharm Sin B 6(4):287-96. [article]

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