Exosomes in Gliomas: Biogenesis, Isolation, and Preliminary Applications in Nanomedicine

Abstract

Exosomes are phospholipid-based particles endogenously produced by both normal and tumor cells. Initially identified as a pathway for shuttling cellular waste, for a long time they were thought to act as "garbage bags", and only in the past few years have they emerged as a promising drug delivery system. In this review, we provide an overview of the knowledge about exosome architecture and biogenesis and the recent progress in isolation methods. Furthermore, we describe the mechanisms involved in both extra- and intracellular communication with a focus on glioma brain tumors. Glioma is considered a rare disease and is the most prominent aggressive brain malignancy. How exosomes target glial tumoral cells in vivo remains largely unknown. However, they are able to influence numerous physio-pathological aspects. Here, we discuss the role they play in this heterogeneous and complex microenvironment and their potential applications.

Keywords: biomarkers; brain diseases; extracellular vesicles; glioma; intercellular communication; miRNA; therapeutics; tumor microenvironment.

Figure 1

Biogenesis and secretion of exosomes. After the endocytosis of the plasma membrane, the transmembrane proteins are sorted into the vesicles that bud from the cellular membrane into “early endosomes” (I). The biogenesis of the exosome begins with the progressive formation and accumulation of ILVs inside MVBs (II). This process is mediated via an ESCRT-dependent (II*) and/or independent (II**) pathway. Then, the MVBs may follow a degradation pathway fusing with lysosomes or are destined to release the ILVs as exosomes to the extracellular space by exocytosis (III).