Modularized Extracellular Vesicles: The Dawn of Prospective Personalized and Precision Medicine

Abstract

Extracellular vesicles (EVs) are ubiquitous nanosized membrane vesicles consisting of a lipid bilayer enclosing proteins and nucleic acids, which are active in intercellular communications. EVs are increasingly seen as a vital component of many biological functions that were once considered to require the direct participation of stem cells. Consequently, transplantation of EVs is gradually becoming considered an alternative to stem cell transplantation due to their significant advantages, including their relatively low probability of neoplastic transformation and abnormal differentiation. However, as research has progressed, it is realized that EVs derived from native‐source cells may have various shortcomings, which can be corrected by modification and optimization. To date, attempts are made to modify or improve almost all the components of EVs, including the lipid bilayer, proteins, and nucleic acids, launching a new era of modularized EV therapy through the “modular design” of EV components. One high‐yield technique, generating EV mimetic nanovesicles, will help to make industrial production of modularized EVs a reality. These modularized EVs have highly customized “modular design” components related to biological function and targeted delivery and are proposed as a promising approach to achieve personalized and precision medicine.

Microfluidics‐based on‐a‐chip systems for isolating and analysing extracellular vesicles

“…To make EVs more versatile rather than limited to their native functions, there have been an increasing number of studies focused on molecular engineering of EVs. The traditional or conventional methods of using engineered EVs as a DDS have been comprehensively reviewed in our previous literature review [123]. Technically speaking, these strategies for EV engineering could be briefly classified into two levels: (1) engineering at the parent cell level – involving manipulation using genetic or metabolic methods; and (2) engineering at the EV level – including surface molecular modification methods and permeabilisation of the membrane.…”

“…However, we believe that bringing the fundamental principles of conventional methods into microfluidic instruments has more potential for such applications. For example, the principles used in conventional methods, including the use of lipophilic/amphipathic molecules, electroporation and combination with liposomes [123], can be combined with the advantages of a microfluidic system such as accurate control of mass transfer [127]. Unfortunately, there have been barely any major breakthroughs in this direction.…”

“…However, there are several disadvantages to the use of synthetic nanoparticles, such as low biocompatibility, immunoreaction and safety problems [50]. In comparison, EV-based DDSs have several advantages, for example, (1) low toxicity[51,52], (2) good stability in the circulation [52,53], (3) specific targeting ability [51,52], (4) customisation of targeting ability by modifying surface proteins, for example, based on the C1C2 domain from the EV-surface-specific protein MFG-E8 (milk fat globule-epidermal growth factor 8 protein), or the N-terminus of lysosomal-associated membrane protein 2b (Lamp2b) [52,54] (Figure 1(e)) and (5) straightforward cargo loading, especially for biomacromolecules, based on cell engineering, which is particularly suitable for delivering nucleic acids, as well as providing specific delivery technology for proteins – for example, intracellular proteins labelled by a WW tag for the recognition by late-domain (L-domain) proteins and specifically loaded into EVs during their biogenesis [9,52] (Figure 1(f)). As a result, we believe that EVs will open up a new frontier in the field of regenerative medicine.…”

Engineered Cell‐Derived Microparticles Bi2Se3/DOX@MPs for Imaging Guided Synergistic Photothermal/Low‐Dose Chemotherapy of Cancer

“…[2][3][4] Moreover, the capacity of transferring bioactive molecules may allow MPs to be used as potential drug delivery systems (DDS) in cancer therapy. [8][9][10][11][12] For example, MPs loaded with different drugs were successfully applied in chemotherapy, [13][14][15] immunotherapy, [16][17][18] or gene therapy [19] of cancers, which have been proved to be effective treatments. [8][9][10][11][12] For example, MPs loaded with different drugs were successfully applied in chemotherapy, [13][14][15] immunotherapy, [16][17][18] or gene therapy [19] of cancers, which have been proved to be effective treatments.…”

Exosome labeling by lipophilic dye PKH26 results in significant increase in vesicle size

“…Exosomes are small-membrane bound vesicles nm in diameter) secreted by all cell types examined and can be found in almost all biofluids including blood, breast milk, urine, saliva and even in cell culture media [1,2]. Exosomes mediate cell-cell communication by exchanging proteins, DNA, RNA and lipids between donor and recipient cells and activating signaling pathways in target cells via receptor ligand interaction [3,4].…”