Perspectives in Manipulating EVs for Therapeutic Applications: Focus on Cancer Treatment

Abstract

Extracellular vesicles (EVs) receive special attention from oncologists due to their assumed usefulness as prognostic markers, vaccines to induce anti-cancer immune response, and physiological delivery tools. The latter application, which supports the reduction of side effects of treatment, is still fraught with many challenges, including established methods for loading EVs with selected cargo and directing them towards target cells. EVs could be loaded with selected cargo either in vitro using several physicochemical techniques, or in vivo by modification of parental cell, which may have an advantage over in vitro procedures, since some of them significantly influence EVs’ properties. Otherwise, our research findings suggest that EVs could be passively supplemented with micro RNAs (miRNAs) or miRNA antagonists to induce expected biological effect. Furthermore, our observations imply that antigen-specific antibody light chains could coat the surface of EVs to increase the specificity of cell targeting. Finally, the route of EVs’ administration also determines their bioavailability and eventually induced therapeutic effect. Besides, EV membrane lipids may possibly possess immune adjuvant activity. The review summarizes the current knowledge on the possibilities to manipulate EVs to use them as a delivery tool, with the special emphasis on anti-cancer therapy.

Uptake and Fate of Extracellular Membrane Vesicles: Nucleoplasmic Reticulum-Associated Late Endosomes as a New Gate to Intercellular Communication

“…We showed that monovalent antibody against CD9 can impede the entry of EVs into melanoma cells [ 91 ]. Further efforts are needed to dissect all mechanisms regulating the specificity of EV-recipient cell interactions, which is an important step to design new strategies based on EVs as a bio-vehicle for therapeutic drug delivery [ 92 , 93 , 94 ].…”

Development of Extracellular Vesicle Therapeutics: Challenges, Considerations, and Opportunities

“…An alternative to modifying parental cells is the direct incorporation of specific molecules (i.e., miRNA, siRNA, protein, lipids, drugs) into EVs through passive or active methods ( Luan et al, 2017 ; Sterzenbach et al, 2017 ; Nasiri Kenari et al, 2020 ; Nazimek and Bryniarski, 2020 ). Incubation of EVs with active components is a passive method of loading that involves the diffusion of drugs or molecules with varied encapsulation efficiency through the EV membrane.…”

Current Perspectives on Clinical Use of Exosomes as a Personalized Contrast Media and Theranostics

“…Surface modification with polyethylene glycol (PEG) is the most common approach among these strategies [ 60 ]. Antigen-specific antibody light chains could coat the surface of EVs to increase cell targeting specificity, while EV membrane lipids may possess immune adjuvant activity [ 62 ]. Engineering EVs to functionalize and enclose molecules or nanoparticles, for imaging or therapy purposes are shown in Figure 3 .…”

“…This could represent a critical advance forward to the disclosing of exosome homing and, more broadly, TEX in pathological conditions. The route of EV administration determines bioavailability and affects its therapeutic effect [ 62 ]. Despite advances in exosome modification strategies, there are still many challenges to overcome to effectively harness their therapeutic potential.…”