Extracellular vesicle-based Nanotherapeutics: Emerging frontiers in anti-inflammatory therapy

Abstract

Dysregulated inflammation is a complicated pathological process involved in various diseases, and the treatment of inflammation-linked disorders currently represents an enormous global burden. Extracellular vesicles (EVs) are nanosized, lipid membrane-enclosed vesicles secreted by virtually all types of cells, which act as an important intercellular communicative medium. Considering their capacity to transfer bioactive substances, both unmodified and engineered EVs are increasingly being explored as potential therapeutic agents or therapeutic vehicles. Moreover, as the nature's own delivery tool, EVs possess many desirable advantages, such as stability, biocompatibility, low immunogenicity, low toxicity, and biological barrier permeability. The application of EV-based therapy to combat inflammation, though still in an early stage of development, has profound transformative potential. In this review, we highlight the recent progress in EV engineering for inflammation targeting and modulation, summarize their preclinical applications in the treatment of inflammatory disorders, and present our views on the anti-inflammatory applications of EV-based nanotherapeutics.

Exosomal miR-125b-5p deriving from mesenchymal stem cells promotes tubular repair by suppression of p53 in ischemic acute kidney injury

“…Generally, the membrane proteins present on EVs allow their targeting and capture by recipient cells. Our previous studies demonstrated that VLA-4 and LFA-1 on the surface of macrophage-derived microvesicles enabled them to adhere to the injured kidney through integrin-mediated adhesive interactions (VLA-4/VCAM-1 and LFA-1/ICAM-1) 24 , 47 . In this study, we found VLA-4 and LFA-1 were expressed on MSC-exos.…”

“…Interestingly, a Phase 3 study with siRNA targeting p53 (QPI-1002) is undergoing to evaluate the prevention for AKI following cardiac surgery ( https://clinicaltrials.gov/ct2/show/NCT03510897 ). Due to the distinct advantages of low immunogenicity, biocompatibility, biological barrier permeability, and stability 14 , 47 , 54 , MSC-exos carrying naturally loaded miR-125b-5p may represent a superior therapeutic strategy of repressing p53 signaling for tubular repair in AKI.…”

Mesenchymal stem cells and extracellular vesicles in therapy against kidney diseases

“…EVs can carry many types of drugs via pre-and post-release modification [33] and play their therapeutic role by loading substances thereon and subsequent targeting [34], such as micro-molecules, proteins, and nucleic acids [35]. EVs have become a research focus as a drug carrier for various diseases, such as carrying antineoplastic [36] and anti-inflammatory [37] drugs. The specificity of uptake of EVs is highly dependent on the surface of EVs and acceptor cells, including integrins, proteoglycans, lectins, glycolipid, and others, which can aid in targeting [38].…”

Therapeutic Application of Exosomes in Inflammatory Diseases

“…Inflammation is involved in the pathogenesis of many diseases; acute or chronic immune responses in target organs can cause functional organ loss. The number of trials studying the therapeutic potential of native or engineered EVs for treating inflammatory diseases is increasing [ 176 , 177 ]. Beginning in 2014, there has been an official movement to establish a guide for the harvest, isolation, characterization, and functional testing of EVs; the guide is now being used as a standard for EV researchers [ 38 , 178 ].…”