Extracellular vesicles: from intracellular trafficking molecules to fully fortified delivery vehicles for cancer therapeutics

Abstract

Extracellular vesicles (EVs) are emerging as viable tools in cancer treatment due to their ability to carry a wide range of theranostic activities. This review summarizes different forms of EVs such as exosomes, microvesicles, apoptotic bodies, and oncosomes. It also sheds the light onto isolation methodologies, characterization techniques and therapeutic applications of all discussed EVs. Evidence indicates that EVs are particularly effective in delivering chemotherapeutic medications, and immunomodulatory agents. However, the advancement of EV-based therapies into clinical practice is hindered by challenges including EVs heterogeneity, cargo loading efficiency, and in vivo stability. Overall, EVs have the potential to change cancer therapeutic paradigms. Continued research and development activities are critical for improving EV-based medications and increasing their therapeutic impact.

Fig. 1. Biogenesis and secretion of different types of extracellular vesicles.

Fig. 2. Isolation of extracellular vesicles using density-based methods (A) differential ultracentrifugation in a two-step manner to eliminate cell debris and proteins, (B) density gradient centrifugation using pre-loaded centrifugal tubes.

Fig. 3. Isolation of extracellular vesicles using size-based methods (A) size exclusion chromatography using columns packed with a porous matrix to retain smaller particles, (B) polymer precipitation where EVs are consequently precipitated at low-speed centrifugation, (C) filtration method employing several filtration membranes.

Fig. 4. Affinity-based and immunoaffinity approach methods (A) enzyme-linked immunosorbent assay (ELISA) where antibodies are used to first capture antigen-expressing EVs then tag the immobilized EVs, (B) magneto-immunoprecipitation using biotinylated antibodies on streptavidin magnetic beads, (C) aptamer-based method to bind specific protein-expressing EVs, (D) lipid-based probe method exploiting EVs' lipid membrane.

Fig. 5. Multifunctional role of extracellular vesicles in cancer therapeutics.