Strategies for Engineering of Extracellular Vesicles

Abstract

Extracellular vesicles (EVs) are membrane vesicles released by cells into the extracellular space. EVs mediate cell-to-cell communication through local and systemic transportation of biomolecules such as DNA, RNA, transcription factors, cytokines, chemokines, enzymes, lipids, and organelles within the human body. EVs gained a particular interest from cancer biology scientists because of their role in the modulation of the tumor microenvironment through delivering bioactive molecules. In this respect, EVs represent an attractive therapeutic target and a means for drug delivery. The advantages of EVs include their biocompatibility, small size, and low immunogenicity. However, there are several limitations that restrict the widespread use of EVs in therapy, namely, their low specificity and payload capacity. Thus, in order to enhance the therapeutic efficacy and delivery specificity, the surface and composition of extracellular vesicles should be modified accordingly. In this review, we describe various approaches to engineering EVs, and further discuss their advantages and disadvantages to promote the application of EVs in clinical practice.

Nanoinjection of extracellular vesicles to single live cells by robotic fluidic force microscopy

“…This single cell nanoinjection technique may enable organelle‐specific targeting of nanoinjected EVs along with their cargo (Figure 7 ). Cells can be engineered to release EVs with surface molecules (Danilushkina et al., 2023 ; Vukman et al., 2020 ; Wang et al., 2023 ) that are known to have a role in organelle targeting (Pfeffer & Aivazian, 2004 ; Saminathan et al., 2022 ; Wu et al., 2010 ) (e.g., various Rab proteins or proteins with known signal sequences). Alternatively, targeting molecules can be conjugated to the surface of EVs using click chemistry (Murphy et al., 2019 ; Ruan et al., 2023 ; Smyth et al., 2014 ) or the nanoinjected EVs can be decorated with targeting proteins by generating an artificial protein corona (Musicò et al., 2023 ; Tóth et al., 2021 ).…”

Extracellular Vesicles and Immunity: At the Crossroads of Cell Communication

“…Furthermore, EVs can lean on their biological camouflage to evade the immune system and reach their target without being recognised as foreign bodies. This camouflage ability, combined with their biocompatible nature, makes EVs a potentially safe and efficient drug delivery system [166].…”

Harnessing Bacterial Extracellular Vesicle Immune Effects for Cancer Therapy

“…For example, mammalian EV circulating time was significantly increased when they were engineered to express the “don't-eat-me” signal, CD47, which inhibits phagocytosis by macrophages upon ligation with its receptor, SIRPα [ 127 ]. Others have modified the surface of EVs and nanoparticles by chemical modification (click chemistry), glycan modification, and insertion of specific peptides to further modify their pharmacokinetic characteristics [ 128 ]. In summary, combinations of optimized administration and engineering strategies are likely to be needed for the effective application of bEVs in cancer therapy.…”