A systematic approach to exosome‐based translational nanomedicine

Abstract

Exosomes are a type of cell-derived extracellular nanovesicle. They relay information between cells. Some known exosome functions include immune modulation, promotion of angiogenesis, and tumor metastasis. To date, clinical use of exosomes has focused predominantly on evaluating their efficacy as cancer vaccines or diagnostically as biomarker containers. However, few investigations have explored their potential to serve as a platform for the development of semi-synthetic nanovesicles. Given their nanoscale size, potential to express targeting ligands in native conformations and deformable structure, exosomes offer a logical biological vesicle platform for adapting and producing semi-synthetic vesicles with excellent potential for nanomedicine applications. However, there are obstacles associated with realizing this potential that must be addressed. Thus, a systematic approach to isolating, modifying, and testing exosomes is presented to facilitate the introduction of exosome-based translational nanomedicine.

Macrophage-secreted Exosomes Delivering miRNA-21 Inhibitor can Regulate BGC-823 Cell Proliferation

“…Multiple miRNAs associated with gastric carcinogenesis display tissue-specific expression, and can function as either tumor suppressors or oncogenes. A number of specific miRNAs are differentially expressed in gastric cancer and normal gastric mucosa: miR-21, miR-34b/c, and miR-221/222 are upregulated gastric tumors, whereas miR-124a, miR-128b, and miR-148 are downregulated (Li et al, 2012;Hood et al, 2012). A clinical study found high miR-21 levels in exosomes from ovarian carcinoma effusion supernatants by qPCR, and these were associated with poor progression-free survival times (Vaksman et al, 2014).…”

Post Isolation Modification of Exosomes for Nanomedicine Applications

“…They relay information between tissue microenvironments [1] and can influence target cell function and differentiation [2]. They contain and protect valuable mRNA and miRNA information which corresponds to source cell normal or pathogenic processes.…”

“…For one, exosomes naturally carry RNA, lipid, protein and metabolite cargo [1,[3][4][5] which enables their use as drug delivery vehicles. Additionally, similar to cells, exosomes contain a deformable cytoskeleton and 'gel-like' cytoplasmderived core [1]. Conceivably, these biophysical properties enhance exosome structural integrity and resistance to rupture during trafficking in vivo.…”

“…Exosomes can function essentially as nanoscale erythrocytes engaged in nanoscale diapedesis. Exosomes being <400 nm in diameter can easily traverse fenestrated capillaries to access tissue sites [1].…”

“…Additional privileged access to tunneling nanotube conduits may further allow exosomes to deliver cargo deep within tissue microenvironments [1,13]. Tunneling nanotubes can transport vesicles between cells and could provide a means for exosomal nanocarriers to uniquely move cargo up concentration gradients which is a difficult feat for synthetic nanocarriers.…”