The Biological Function and Therapeutic Potential of Exosomes in Cancer: Exosomes as Efficient Nanocommunicators for Cancer Therapy

Abstract

Cancer therapeutics must be delivered to their targets for improving efficacy and reducing toxicity, though they encounter physiological barriers in the tumor microenvironment. They also face limitations associated with genetic instability and dynamic changes of surface proteins in cancer cells. Nanosized exosomes generated from the endosomal compartment, however, transfer their cargo to the recipient cells and mediate the intercellular communication, which affects malignancy progression, tumor immunity, and chemoresistance. In this review, we give an overview of exosomes' biological aspects and therapeutic potential as diagnostic biomarkers and drug delivery vehicles for oncotherapy. Furthermore, we discuss whether exosomes could contribute to personalized cancer immunotherapy drug design as efficient nanocommunicators.

Keywords: cancer; diagnostic biomarker; drug delivery vehicle; exosome; nanocommunicator; personalized cancer immunotherapy.

Figure 1

The process of exosome biogenesis. The perimeter membrane of endocytic vesicles buds inward during endosome maturation from the early endosome to the late endosome. Further invagination of the endosomal membrane forms intraluminal vesicles (ILVs) in the multivesicular body (MVB). Subsequently, the MVB is fused with the lysosome or release its contents in the form of exosomes (top right). This process of exosome biogenesis is different from that of microvesicle (MV) shedding (bottom). Receptors internalized from the cell surface and other exosomal cargo proteins are packed in the late endosome either by endosomal sorting complex required for transport (ESCRT)-dependent or ESCRT-independent pathway. ER: endoplasmic reticulum; ILV: intraluminal vesicle; MVB: multivesicular body; MV: microvesicle; ESCRT: endosomal sorting complex required for transport; ALIX: apoptosis-linked gene 2-interacting protein X.

Figure 2

The illustration of exosome–cell interaction. Exosomes can be taken up into the recipient cell via direct membrane fusion or endocytosis, leading to the delivery of exosomal contents such as DNAs, messenger RNAs, long non-coding RNAs, enzymes, and signaling peptides or proteins to the cytosolic space of the recipient cell. Receptor-ligand interactions between cell surface receptors and exosomal ligands may also occur.

Figure 3

The illustration of exosomal components. The diverse functions of exosomes are governed by the delivery of exosomal cargo proteins and nucleic acids to the recipient cells. Exosomal components include lipids, nucleic acids, tetraspanins, adhesion molecules, antigen-presenting molecules, transmembrane receptors, MVB formation proteins, membrane trafficking proteins, enzymes, signaling proteins, etc. mRNA: messenger RNAs; lncRNA: long non-coding RNA; ICAM: intercellular adhesion molecule; EpCAM: epithelial cell adhesion molecule; MHC: major histocompatibility complex.

Figure 4

Potential therapeutic applications of exosomes in cancer. As exosomal components reflect the characteristics of the cells of origin, many attempts have been made to use tumor-derived exosomes (TEXs) as cancer diagnostic biomarkers. For identification of exosome contents, general methods such as polymerase chain reaction (PCR), next-generation sequencing (NGS), and proteomics can be used. Exosomes also have therapeutic potential as nanovehicles for drug delivery and personalized cancer immunotherapy. TEX: tumor-derived exosome; PCR: polymerase chain reaction; NGS: next-generation sequencing.