Exosomes: A Novel Strategy for Treatment and Prevention of Diseases

Abstract

An "exosome" is a nanoscale membrane vesicle derived from cell endocytosis that functions as an important intercellular communication mediator regulating the exchange of proteins and genetic materials between donor and surrounding cells. Exosomes secreted by normal and cancer cells participate in tumor initiation, progression, invasion, and metastasis. Furthermore, immune cells and cancer cells exert a two-way bidirectional regulatory effect on tumor immunity by exchanging exosomes. Current studies on exosomes have further expanded their known functions in physiological and pathological processes. The purpose of this review is to describe their discovery and biological functions in the context of their enormous potential in the clinical diagnosis, prevention, and treatment of cancer as well as bacterial and viral infectious diseases.

Keywords: cancer; diagnosis index; drug delivery; exosomes; pathogenic microorganism; vesicles.

FIGURE 1

Biogenesis and transport of different extracellular vesicles (EVs). (A) The formation of an early endosome. (B) The development of an early exosome into a late endosome (multivesicular body, MVB). The inward budding allows packing of cytosolic contents in the intraluminal vesicles. (C) The fusion of mature MVBs and lysosome to degrade the vesicle cargo. (D) MVBs can also fuse with the plasma membrane to release their intraluminal vesicles (as exosomes). (E) Secretion of exosomes into the extracellular environment. (F) Other microvesicles can be secreted through direct budding from the plasma membrane of the host cell. There are at least three mechanisms by which EVs interact with recipient cells: (G) direct fusion with the plasma membrane of the recipient cell; (H) receptor-mediated endocytosis following receptor–ligand interaction between EVs and the recipient cell; and (I) signaling via direct interactions of the receptor and its ligand on the recipient cell surface.

FIGURE 2

The role of exosomes in bacterial, parasitic, or viral infections. (A) Virus-derived exosomes contain proteins and RNAs that act on specific DNA regions and not only regulate gene expression in host cells, but also alter their survival condition. (B) Virus-secreted exosomes transfer trans-activating RNA (TAR-RNA) to stimulate expression of intracellular pro-inflammatory cytokines. (C) Bacteria and parasites can transfer DNA that encodes drug-resistance to other pathogens, thereby promoting the growth of pathogens. Moreover, an infected cell can use such communication as a defense mechanism.

FIGURE 3

The function of exosomes in cancer cell behavior and tumor microenvironment. (A) Tumor-derived exosomes can promote tumor formation by regulating the synthesis of cell-independent microRNA (miRNA). (B) Cancer cells secrete exosomes to modulate the tumor microenvironment. (C) Tumor-derived exosomes direct metastatic organotropism of cancer cells.

FIGURE 4

The function of exosomes in immune regulation.