{"title":"Visualization strategies of extracellular vesicles: Illuminating the invisible ‘dust’ in theranostics","authors":"Kaiyue Zhang , Jingxuan Hu , Yilan Hu","doi":"10.1016/j.vesic.2024.100061","DOIUrl":"10.1016/j.vesic.2024.100061","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), lipid bilayer vesicles with diameters of 30-150 nm derived from nearly all cell types, were once dismissed as “platelet dust” but are now recognized as key mediators of intercellular communication, playing vital roles in both physiological and pathophysiological processes. However, the clinical applications of EVs in theranostics remain limited by the challenge of effectively visualizing them at high resolution both <em>in vitro</em> and <em>in vivo</em>, primarily due to their nanoscale size. To address this limitation, researchers worldwide are developing innovative methods for labeling and visualizing EVs, aiming to unlock their full potential in optimized theranostic applications. This review provides a comprehensive overview of current strategies for EV labeling across various experimental settings and highlights their promising theranostic applications of diverse diseases.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100061"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143097288","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Prospects and challenges of targeted extracellular vesicles drug delivery for cancer treatment","authors":"Fatemeh Maher , Ali Samadi , Peyman Asadi , Isabella Jodoin","doi":"10.1016/j.vesic.2024.100059","DOIUrl":"10.1016/j.vesic.2024.100059","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) have the ability to alter the phenotypes and functions of other cells as well as reflect the state of the cell from whence they originated.</div><div>Extracellular vesicles, or EVs, are membrane-bound nanostructures released into the extracellular environment. Under both normal and pathological circumstances, they are widely discharged from cells and display a variety of sizes, contents, and surface marks. These EVs are abundant in human serum, yet it might be difficult to separate them from non-EV lipid particles and serum proteins. These vesicles influence several physiological and pathological processes, including those that occur in the tumor microenvironment (TME), by transporting different cellular constituents such as proteins, mRNAs, miRNAs, DNA, and lipids across distances. EVs are potential possibilities for therapeutic agents, medication delivery methods, and disease biomarkers due to their crucial functions in cellular communication. EV detection has the potential to serve as a diagnostic biomarker and can facilitate early identification, particularly in the context of cancer diagnosis. Furthermore, EV subtypes may be clinically significant as different subtypes are emerging as targeted medication delivery methods. There is still a need for non-invasive biomarkers to track biological processes for treatment and diagnosis. In the future, utilizing EVs' distinct composition may open up new possibilities for enhanced diagnosis and treatment.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100059"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143096973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sahimy Ayus-Martinez , William Meza-Morales , Jesus Jimenez-Osorio , Maria Buendia-Otero , Luis López , Lisandro Cunci , Donald O. Freytes , Camilo Mora
{"title":"From isolation to detection, advancing insights into endothelial matrix-bound vesicles","authors":"Sahimy Ayus-Martinez , William Meza-Morales , Jesus Jimenez-Osorio , Maria Buendia-Otero , Luis López , Lisandro Cunci , Donald O. Freytes , Camilo Mora","doi":"10.1016/j.vesic.2024.100060","DOIUrl":"10.1016/j.vesic.2024.100060","url":null,"abstract":"<div><div>Matrix-bound vesicles (MBVs), an integral part of the extracellular matrix (ECM), are emerging as pivotal factors in ECM-driven molecular signaling. This study is the first to report the isolation of MBVs from porcine arterial endothelial cell basement membranes (A-MBVs) and thyroid cartilage (C-MBVs), the latter serving as a negative control due to its minimal vascular characteristics. Using Transmission Electron Microscopy (TEM), Nano-Tracking Analysis (NTA), Electrochemical Impedance Spectroscopy (EIS), and Atomic Force Microscopy (AFM), we orthogonally characterized the isolated MBVs. We detected the presence and preservation of vascular endothelial cadherin (CD144) in A-MBVs, its low to non-detetcted in C-MBVs, in which SOX9, a chondrocyte marker, was detected. Moreover, we developed a prototype of an immuno-functionalized screen-printed electrode designed for the immunoadsorption of CD144+ MBVs. This device facilitated the electrochemical detection of the targeted vesicles and allowed for their subsequent topological characterization using AFM, which verified the integrity and morphology of CD144+ MBVs post-immunoadsorption. These advancements enhance our comprehension of MBVs as conveyors of tissue-specific signals and pioneer new avenues for harnessing their cargo in biomedical applications. This research sets a significant precedent for future studies on the application of MBVs in regenerative medicine and ECM signaling.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100060"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11759483/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143048614","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Novel administration strategies for tissue-specific delivery of extracellular vesicles","authors":"Junyao Deng , Qishan Li , Fei Wang","doi":"10.1016/j.vesic.2024.100057","DOIUrl":"10.1016/j.vesic.2024.100057","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are nanoparticles released by cells with bilayer lipid membranes that have been demonstrated to regulate biological activities. The potential of EVs as a novel therapeutic or drug delivery platform has already been identified in emerging research. The therapeutic efficacy of EVs is contingent upon the quantity of EVs internalized by target cells, which necessitates the enhanced retention of EVs in target organs. Accordingly, various novel administration strategies for the targeted delivery of therapeutic EVs into specific tissues were developed. This review presents a comprehensive overview of the latest developments in EV delivery routes for brain-, heart-, lung-, skin-, eye-, and gastrointestinal tract-specific applications. We believe that the emergence of innovative EV administration strategies will contribute to the future clinical trials and eventual applicability of EV-based therapeutics.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100057"},"PeriodicalIF":0.0,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142720069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Linda Hofmann , Robin Lochbaum , Lutz Schütt , Ralph Röth , Stefanie Schmitteckert , Barbara Wollenberg , Thomas K. Hoffmann , Cornelia Brunner , Jens Greve , Janina Hahn , Marie-Nicole Theodoraki
{"title":"Characterization of plasma-derived small extracellular vesicle miRNA and protein cargo in hereditary angioedema","authors":"Linda Hofmann , Robin Lochbaum , Lutz Schütt , Ralph Röth , Stefanie Schmitteckert , Barbara Wollenberg , Thomas K. Hoffmann , Cornelia Brunner , Jens Greve , Janina Hahn , Marie-Nicole Theodoraki","doi":"10.1016/j.vesic.2024.100056","DOIUrl":"10.1016/j.vesic.2024.100056","url":null,"abstract":"<div><div>Hereditary angioedema (HAE) is an inherited disorder causing attacks of subcutaneous tissue or mucosa swelling. The disease burden and attack frequencies vary significantly among patients. This is the first pilot study investigating small extracellular vesicles (sEV) as potential disease modulators in HAE.</div><div>Plasma-derived sEVs from HAE patients and healthy donors (HD) were thoroughly characterized by Western blot, transmission electron microscopy, nanoparticle tracking and bead-based flow cytometry. The miRNA content of sEVs was examined by nCounter technology and used to predict sEV-based pathomechanisms <em>in silico</em>. All sEV readouts were analyzed regarding HAE-related changes and associations with clinical parameters and attack frequency.</div><div>Total sEV protein levels were elevated in HAE patients compared to HD. In HAE patients, lower levels of sEVs carrying CD8, CD209, CD81, CD24 and CD44 were measured. sEV miRNA profiling revealed 84 HAE-exclusive and 30 significantly HAE-upregulated candidates. Core hubs of their predicted interaction networks were AGO2, VEGF, RGS5, MTA1, IFG1 and BAX. A set of 12 and 36 sEV miRNAs were restricted to patients with absent attacks or patients with present attacks during prophylactic therapy, respectively.</div><div>sEVs, especially sEV miRNAs, could contribute to disease pathogenesis and differential attack frequencies. They emerged as disease modulators in HAE and require further study to reveal underlying mechanisms.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100056"},"PeriodicalIF":0.0,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142657127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fan Yang , Zewen Wang , Mingjian Wu, Jingyi Xu, Junlei Li, Jiahe Liu, Ting He, Tao Zhang, Baoyi Liu
{"title":"Application of miR-29a-Exosome and multifunctional scaffold for full-thickness cartilage defects","authors":"Fan Yang , Zewen Wang , Mingjian Wu, Jingyi Xu, Junlei Li, Jiahe Liu, Ting He, Tao Zhang, Baoyi Liu","doi":"10.1016/j.vesic.2024.100055","DOIUrl":"10.1016/j.vesic.2024.100055","url":null,"abstract":"<div><h3>Background</h3><div>Full-thickness cartilage defect is a common refractory disease in orthopedics. In this study, we designed a novel composite scaffold composed of silk fibroin-chitosan for the cartilage layer and porous tantalum for the subchondral bone layer, loaded with engineered bone mesenchymal stem cell exosomes, to evaluate its efficacy in repairing full-thickness cartilage defect.</div></div><div><h3>Methods</h3><div>Porous tantalum was 3D printed and combined with silk fibroin-chitosan to form a composite scaffold. Chondrocytes were cultured on the scaffold, and their growth was assessed using the CCK-8 method. Toluidine blue staining confirmed cell morphology, while immunofluorescence revealed collagen type Ⅱ expression. Engineered exosomes loaded with miR-29a were created and characterized using various techniques. Co-culturing with chondrocytes demonstrated their proliferation over 10 days. Immunofluorescence revealed staining for the nucleus, collagen type II, and Aggrecan. In vivo experiments were performed on rats to assess cartilage defect repair, utilizing histological staining and micro-CT scanning at 4 and 8 weeks post-operation.</div></div><div><h3>Results</h3><div>The silk fibroin-chitosan scaffold demonstrated good biocompatibility, supporting chondrocyte adhesion, growth, and cartilage tissue formation. Engineered exosomes exhibited promising biological activity, conducive to bone and cartilage regeneration. The implantation of the silk fibroin-chitosan/porous tantalum composite scaffold loaded with engineered exosomes promoted integration with the surrounding bone and cartilage tissues, facilitating repair and regeneration.</div></div><div><h3>Conclusions</h3><div>The silk fibroin-chitosan combined with porous tantalum scaffold carrying engineered exosomes loaded with miR-29a has good potential for full-thickness cartilage defects regeneration.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100055"},"PeriodicalIF":0.0,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142593391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Carla Martin Perez , Xiuming Liang , Dhanu Gupta , Emily R. Haughton , Mariana Conceição , Imre Mäger , Samir EL Andaloussi , Matthew J.A. Wood , Thomas C. Roberts
{"title":"An extracellular vesicle delivery platform based on the PTTG1IP protein","authors":"Carla Martin Perez , Xiuming Liang , Dhanu Gupta , Emily R. Haughton , Mariana Conceição , Imre Mäger , Samir EL Andaloussi , Matthew J.A. Wood , Thomas C. Roberts","doi":"10.1016/j.vesic.2024.100054","DOIUrl":"10.1016/j.vesic.2024.100054","url":null,"abstract":"<div><div>Extracellular vesicles (EVs) are promising therapeutic delivery vehicles, although their potential is limited by a lack of efficient engineering strategies to enhance loading and functional cargo delivery. Using an in-house bioinformatics analysis, we identified N-glycosylation as a putative EV-sorting feature. PTTG1IP (a small, N-glycosylated, single-spanning transmembrane protein) was found to be a suitable scaffold for EV loading of therapeutic cargoes, with loading dependent on its N-glycosylation at two arginine residues. Chimeric proteins consisting of PTTG1IP fused with various cargo proteins, and separated by self-cleaving sequences (to promote cargo release), were shown to enable highly efficient functional delivery of Cre protein to recipient cell cultures and mouse xenograft tumors, and delivery of Cas9-sgRNA complexes to recipient reporter cells. The favorable membrane topology of PTTG1IP enabled facile engineering of further variants with improved properties, highlighting its versatility and potential as a platform for EV-based therapeutics.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100054"},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142530087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ruotong Huang , Jiajun Zhu , Ru Fan , Yiting Tang , Lianlong Hu , HaeJu Lee , Shuying Chen
{"title":"Extracellular vesicle-based drug delivery systems in cancer","authors":"Ruotong Huang , Jiajun Zhu , Ru Fan , Yiting Tang , Lianlong Hu , HaeJu Lee , Shuying Chen","doi":"10.1016/j.vesic.2024.100053","DOIUrl":"10.1016/j.vesic.2024.100053","url":null,"abstract":"<div><div>Extracellular vesicles are lipid bilayer-enclosed extracellular membrane vesicles secreted from cells that have gradually shown promise in cancer treatment. As an essential intercellular communication mediator, extracellular vesicles carry bioactive molecules including proteins, lipids, and nucleic acids, which aid in the control and reprogramming of cell signals and ultimately accelerate the spread of cancer. Simultaneously, extracellular vesicles have become a highly desirable option for drug delivery carriers because of the special capacity to cross boundaries and low immunogenicity. Bypassing the endosomal pathway and lysosomal degradation, they can provide medications directly, increasing their effectiveness and decreasing their negative effects. We review the extracellular vesicles’ development, drug loading techniques, and discuss their potential in clinical applications to provide new avenues for precise and targeted treatment strategies. Additionally, engineering modifications of extracellular vesicles can enhance their ability to target specific cells, improving the stability and effectiveness of cargoes, further driving the development of cancer therapy. In this review, we particularly highlight new therapeutic applications of extracellular vesicles, including the latest progress in extracellular vesicle vaccines in tumors. Nonetheless, there are still a lot of obstacles to be overcome before extracellular vesicles may be used to treat cancer. Future research needs to focus on the characteristics of extracellular vesicles from various sources and explore their specific roles in disease treatment to fully leverage the potential of extracellular vesicles in clinical applications such as drug delivery.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100053"},"PeriodicalIF":0.0,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yundi Chen , Le Wang , Xu Yu , Wenjun Mao , Yuan Wan
{"title":"Ultrasonication outperforms electroporation for extracellular vesicle cargo depletion","authors":"Yundi Chen , Le Wang , Xu Yu , Wenjun Mao , Yuan Wan","doi":"10.1016/j.vesic.2024.100052","DOIUrl":"10.1016/j.vesic.2024.100052","url":null,"abstract":"<div><div>Extracellular vesicles (EVs), submicron-sized membranous structures released by cells, serve as vehicles of tissue-specific proteins and nucleic acids, facilitating intercellular communication and playing roles in pathophysiological processes. Leveraging their unique characteristics, EVs have emerged as promising drug delivery nanocarriers. Electroporation (EP) and ultrasonication (US) are among the prevalent techniques used for loading exogenous drugs into EVs owing to their simplicity and efficiency. However, the effectiveness of the two methods in depleting initial EV cargo has been overlooked. But this information is indispensable, as the bioactive residuals of EVs, notably derived from tumor or stem donor cells, may impact downstream therapeutic effects. Bridging this knowledge gap, therefore, can guide the selection of optimal drugs and loading methods tailored to therapeutic objectives. Here, we used high-throughput sequencing to investigate the protein and small RNA cargo of EVs treated with EP and US, respectively. We found that US exhibits higher efficacy in depleting EV cargo compared to EP, while US may also deplete essential endogenous molecules for combination therapy. Neither method demonstrated significant selectivity in cargo depletion, but they might preferentially retain few specific molecules. Additionally, membrane proteins are more prone to loss during US and EP treatments than cytoplasmic proteins.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100052"},"PeriodicalIF":0.0,"publicationDate":"2024-10-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142424307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wuli Guo , Qi Shu , Lina Gao, Na Gao, Zhen Wang, Wenjing Wei, Yuhan Zhang, Ting Huyan, Qi Li
{"title":"A bibliometric analysis of extracellular vesicles as drug delivery vehicles in disease treatment (2010–2024)","authors":"Wuli Guo , Qi Shu , Lina Gao, Na Gao, Zhen Wang, Wenjing Wei, Yuhan Zhang, Ting Huyan, Qi Li","doi":"10.1016/j.vesic.2024.100051","DOIUrl":"10.1016/j.vesic.2024.100051","url":null,"abstract":"<div><div>To comprehensively summarize the progress of utilizing extracellular vesicles (EVs) as drug delivery vehicles in disease treatment, bibliometric and visualization tools were employed to analyze and exhibit the key information from 6515 literatures that collected by searching “drug delivery” and “extracellular vesicles”, as well as “drug delivery” and “exosomes” as the keywords in Web of Science Core Collection. The obtained articles are from 90 countries/regions, 3343 institutions, 17,989 authors, and 591 journals. Among them, the “nanoparticles”, “cancer” and “biomarkers” are the keywords with the highest frequency. According to experimental articles, EVs are mainly used in the treatment of cancer as drug vehicles.</div></div>","PeriodicalId":73007,"journal":{"name":"Extracellular vesicle","volume":"4 ","pages":"Article 100051"},"PeriodicalIF":0.0,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318709","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}