Biosensors and Bioelectronics, Год журнала: 2023, Номер 245, С. 115856 - 115856
Опубликована: Ноя. 18, 2023
Язык: Английский
Cells, Год журнала: 2021, Номер 10(8), С. 1959 - 1959
Опубликована: Авг. 1, 2021
Exosomes are a type of extracellular vesicles, produced within multivesicular bodies, that then released into the space through merging body with plasma membrane. These vesicles secreted by almost all cell types to aid in vast array cellular functions, including intercellular communication, differentiation and proliferation, angiogenesis, stress response, immune signaling. This ability contribute several distinct processes is due complexity exosomes, as they carry multitude signaling moieties, proteins, lipids, surface receptors, enzymes, cytokines, transcription factors, nucleic acids. The favorable biological properties exosomes biocompatibility, stability, low toxicity, proficient exchange molecular cargos make prime candidates for tissue engineering regenerative medicine. Exploring functions payloads can facilitate regeneration therapies provide mechanistic insight paracrine modulation activities. In this review, we summarize current knowledge exosome biogenesis, composition, isolation methods. We also discuss emerging healing exosomal cargos, such microRNAs, brain injuries, cardiovascular disease, COVID-19 amongst others. Overall, review highlights burgeoning roles potential applications
Язык: Английский
Процитировано
370
Biosensors and Bioelectronics, Год журнала: 2021, Номер 197, С. 113805 - 113805
Опубликована: Ноя. 15, 2021
Язык: Английский
Процитировано
300
Molecular Therapy, Год журнала: 2023, Номер 31(5), С. 1225 - 1230
Опубликована: Янв. 25, 2023
Extracellular vesicles (EVs) are esteemed as a promising delivery vehicle for various genetic therapeutics. They relatively inert, non-immunogenic, biodegradable, and biocompatible. At least in rodents, they can even transit challenging bodily hurdles such the blood-brain barrier. Constitutively shed by all cells with potential to interact specifically neighboring distant targets, EVs be engineered carry deliver therapeutic molecules proteins RNAs. thus emerging an elegant vivo gene therapy vector. Deeper understanding of basic EV biology—including cellular production, loading, systemic distribution, cell delivery—is still needed effective harnessing these endogenous nanoparticles next-generation nanodelivery tools. However, perfect product will produce at clinical scale. In this regard, we propose that vector transduction technologies used convert either ex or directly into factories stable, safe modulation expression function. Here, extrapolate from current state art bright future using treat diseases refractory All eukaryotic release abundance extracellular (EVs): membrane-bound roughly spherical range diameter around 50 500 nm.1Wang W. Li M. Chen Z. Xu L. Chang Wang K. Deng C. Gu Y. Zhou S. Shen et al.Biogenesis function pathophysiological processes skeletal muscle atrophy.Biochem. Pharmacol. 2022; 198: 114954https://doi.org/10.1016/j.bcp.2022.114954Crossref Scopus (15) Google Scholar diverse, categorized not only size but also origin, mode release, molecular composition, Classical subtypes like "ectosomes" (plasma membrane origin) "exosomes" (endosomal may important biology level belie incredible diversity difficult distinguish after leave cell.2Buzas E.I. The roles immune system.Nat. Rev. Immunol. : 1-15https://doi.org/10.1038/s41577-022-00763-8Crossref (23) thought cell-to-cell communications delivering nucleic acids, proteins, small molecules, lipids between cells,3Li S.P. Lin Z.X. Jiang X.Y. Yu Exosomal cargo-loading synthetic exosome-mimics tools.Acta Sin. 2018; 39: 542-551https://doi.org/10.1038/aps.2017.178Crossref PubMed (182) other modes interaction envisioned. Notably, have been observed retain their recipient following being transported EVs, suggesting containing active RNAs, DNAs alter producer cells. These characteristics confer unparalleled terms safety biocompatibility; such, subject extensive experimentation captured interest both public private sectors.4Yang Wu S.Y. advances challenges utilizing exosomes cancer therapeutics.Front. 9: 735https://doi.org/10.3389/fphar.2018.00735Crossref (28) To date, several biomolecules repeatedly loaded delivered target experimentally validated vitro models. RNA therapeutics offer distinct advantages over zinc finger CRISPR therapeutics, RNAs pathways transient manner programmable easy engineer specific diseases, generally immunogenic, is unfortunately case many recombinant protein technologies. Various biotypes biological functions potential, interfering (siRNAs), discovered investigated, leading development new classes drugs.5Damase T.R. Sukhovershin R. Boada Taraballi F. Pettigrew R.I. Cooke J.P. limitless Bioeng. Biotechnol. 2021; 628137https://doi.org/10.3389/fbioe.2021.628137Crossref (136) impart short-term longer-term epigenetic silencing, which based on target, e.g., targeting promoters induce transcriptional silencing.6Weinberg M.S. Morris K.V. Transcriptional silencing humans.Nucleic Acids Res. 2016; 44: 6505-6517https://doi.org/10.1093/nar/gkw139Crossref (61) mRNA-based vaccines now effectively combat COVID-19 pandemic.7Kiaie S.H. Majidi Zolbanin N. Ahmadi A. Bagherifar Valizadeh H. Kashanchi Jafari Recent mRNA-LNP therapeutics: immunological pharmacological aspects.J. Nanobiotechnology. 20: 276https://doi.org/10.1186/s12951-022-01478-7Crossref (3) although rapidly altered produced, must reach intended effective. For example, lipid (LNPs) Pfizer-BioNTech vaccine treatment polyneuropathy targeted liver, approaches cytotoxic, unstable circulation, unsuited tissues.8Hou X. Zaks T. Langer Dong Lipid mRNA delivery.Nat. Mater. 6: 1078-1094https://doi.org/10.1038/s41578-021-00358-0Crossref (455) Moreover, subcellular RNA-based drugs formidable challenge, less than 1% payloads reaching cytosol cell.9Maugeri Nawaz Papadimitriou Angerfors Camponeschi Na Hölttä Skantze P. Johansson Sundqvist al.Linkage endosomal escape LNP-mRNA loading transport cells.Nat. Commun. 2019; 10: 4333https://doi.org/10.1038/s41467-019-12275-6Crossref (123) Potentially, packaging naturally RNA, could safer more physiologically approach. As attempts made integrate species optimize efficiency. While system, it has proven load cargo EVs. during biogenesis isolation physical chemical methods. Electroporation acids EVs; however, deteriorates intrinsic properties causes loss.10Johnsen K.B. Gudbergsson J.M. Skov M.N. Christiansen G. Gurevich Moos Duroux Evaluation electroporation-induced adverse effects adipose-derived stem exosomes.Cytotechnology. 68: 2125-2138https://doi.org/10.1007/s10616-016-9952-7Crossref (94) most common method transfect EV-producer plasmids encoding mRNA. resulting high concentration cytoplasmic sufficient cause perhaps because found functionally export components vast surplus.11Shrivastava multifunctionality exosomes; garbage bin next generation therapy.Genes (Basel). 12: 173https://doi.org/10.3390/genes12020173Crossref (4) Villamizar al. transfected mesenchymal (MSCs) plasmid transcription factor CFTR promoter cystic fibrosis (called CFZF). CFZF, plasmid's CMV promoter, was detect CFZF isolated EVs.12Villamizar O. Waters S.A. Scott Grepo Jaffe Mesenchymal Stem Cell exosome Zinc Finger Protein activation transmembrane conductance regulator.J. Extracell. Vesicles. e12053https://doi.org/10.1002/jev2.12053Crossref (13) increase output, Kojima catalase system called EXOtic,13Kojima Bojar D. Rizzi Hamri G.C.E. El-Baba M.D. Saxena Ausländer Tan K.R. Fussenegger Designer produced implanted intracerebrally Parkinson's disease treatment.Nat. 1305https://doi.org/10.1038/s41467-018-03733-8Crossref (297) consisting construct CD63, protein, plus L7Ae archaeal ribosomal selectively binds C/D box structure. Next, introduced 3′ UTR gene. When were constructs, efficiently packed transferred vitro.13Kojima A tricistronic three genes involved (STEAP3, SDC4, L-aspartate oxidase) EXOtic release. Introduced mouse models disease, transgressed barrier reduced reactive oxygen brain. constitutively mutant gap junction Connexin 43 (Cx43) included. This responsible forming gap-junction structures fusion two connexon hemichannels, allowing intercommunication transfer materials.14Soares A.R. Martins-Marques Ribeiro-Rodrigues Ferreira J.V. Catarino Pinho M.J. Zuzarte Isabel Anjo Manadas B. P G Sluijter J. al.Gap junctional Cx43 communication mammalian cells.Sci. Rep. 2015; 5: 13243https://doi.org/10.1038/srep13243Crossref (119) It expressed Cx present hexamers organized hemichannel structures.14Soares Scholar,15Gemel Kilkus Dawson Beyer E.C. Connecting connexins.Cancers 11: 476https://doi.org/10.3390/cancers11040476Crossref efficiency upon contact.12Villamizar Scholar,16Shrivastava Ray R.M. Holguin Echavarria T.A. Burnett Exosome-mediated stable repression HIV-1.Nat. 5541https://doi.org/10.1038/s41467-021-25839-2Crossref (16) Indeed, CD63-fused appears require co-transfection booster plasmid, Cx43, LAMP2b-fused brain module nluc-C/D Another generate lipid-coated particles purified through mixing-induced partitioning.17Sato Y.T. Umezaki Sawada Mukai Sasaki Harada Shiku Akiyoshi Engineering hybrid liposomes.Sci. 21933https://doi.org/10.1038/srep21933Crossref (333) Scholar,18Li Y.J. J.Y. Liu Qiu Huang Hu X.B. Xiang D.X. Artificial translational nanomedicine.J. 19: 242https://doi.org/10.1186/s12951-021-00986-2Crossref (62) expected, process leads slight decrease numbers, efficient accurate (>90%).19Tsai S.J. Atai N.A. Cacciottolo Nice Salehi Guo Sedgwick Kanagavelu Gould SARS-CoV-2 immunity.J. Biol. Chem. 297: 101266https://doi.org/10.1016/j.jbc.2021.101266Abstract Full Text PDF purification need pre-coat introduces expense time constraints. Therefore, while research purposes, prove scale commercial applications. MicroRNAs (miRNAs) well known modulate types.20Simeoli Montague Jones H.R. Castaldi Chambers Kelleher J.H. Vacca V. Pitcher Grist Al-Ahdal al.Exosomal including microRNA regulates sensory neuron macrophage nerve trauma.Nat. 2017; 8: 1778https://doi.org/10.1038/s41467-017-01841-5Crossref (155) direct interactions Argonaut 2 (AGO2), packaged EVs.21Beltrami Clayton Newbury L.J. Corish Jenkins R.H. Phillips A.O. Fraser D.J. Bowen Stabilization urinary association argonaute protein.Noncoding. RNA. 1: 151-166https://doi.org/10.3390/ncrna1020151Crossref (35) Alternatively, particular YBX1, implicated miRNAs EVs,22Liu X.M. Ma Schekman Selective sorting microRNAs phase-separated YBX1 condensates.Elife. e71982https://doi.org/10.7554/eLife.71982Crossref others suggested there motif pathway miRNA recruitment EVs.23Hung M.E. Leonard J.N. platform actively elucidate limiting steps EV-mediated delivery.J. 31027https://doi.org/10.3402/jev.v5.31027Crossref (112) Yet does appear EVs.24Albanese Y.F.A. Hüls Gärtner Tagawa Mejias-Perez E. Keppler O.T. Göbel Zeidler Shein al.MicroRNAs minor constituents rarely cells.PLoS Genet. 17: e1009951https://doi.org/10.1371/journal.pgen.1009951Crossref (40) Due large genes, significantly phenotype cell, therefore high-value promote, trigger, diseases. Simeoli among first describe neurons macrophages presence capsaicin.20Simeoli Capsaicin incubation injury miRNA-21 milk fat globule-EGF 8 MFG-E8, uptake. authors demonstrated derived capsaicin-treated taken up readily untreated control promoted inflammatory 13Kojima Scholarphenotypes miR-21 macrophages. Activated likely move toward sites where EV-releasing situated, demonstrating existence importance intercellular mediated miRNAs.20Simeoli EV-transferred promoting metastasis, drug resistance, proliferation, inflammation.25Dilsiz Role exosomal cancer.Future Sci. OA. 2020; FSO465https://doi.org/10.2144/fsoa-2019-0116Crossref (60) EV-loaded pathways, seem preferentially relative types, exists within AGO2 RNA-binding EVs.26McKenzie A.J. Hoshino Hong N.H. Cha Franklin J.L. Coffey R.J. Patton J.G. Weaver A.M. KRAS-MEK signaling controls Ago2 exosomes.Cell 15: 978-987https://doi.org/10.1016/j.celrep.2016.03.085Abstract (251) profound regulatory natural occurrence AGO2-binding shRNAs great candidates class circRNAs.27Li Zheng Q. Bao Zhao He Circular enriched exosomes: biomarker diagnosis.Cell 25: 981-984https://doi.org/10.1038/cr.2015.82Crossref (1462) circRNAs single-stranded circular non-coding back splicing exons mRNAs.28Conn Pillman K.A. Toubia Conn V.M. Salmanidis C.A. Roslan Schreiber A.W. Gregory P.A. Goodall G.J. binding quaking formation circRNAs.Cell. 160: 1125-1134https://doi.org/10.1016/j.cell.2015.02.014Abstract (1298) Scholar,29Ragan Shirokikh N.E. Preiss Insights exonic RNA.Sci. 2048https://doi.org/10.1038/s41598-018-37037-0Crossref (74) Some express times amount circRNA compared protein-coding mRNA, functional role, includes regulation absorbing miRNAs, competition pre-mRNA splicing, and, rarely, templates translation.30Meng Feng Tang CircRNA: novel cancer.Mol. Cancer. 16: 94https://doi.org/10.1186/s12943-017-0663-2Crossref (978) lack 5′ ends protects degradation exonucleases, ultimately confers longer lifespan transcripts cytoplasm RNAs.31Liu Khanabdali Kalionis Tai Xia RNAs: isolation, characterization role diseases.RNA 14: 1715-1721https://doi.org/10.1080/15476286.2017.1367886Crossref (78) confirmed negative relation proliferation concentration, allegedly diluted daughter proliferation. Recently, ratio linear higher cells, indicating mechanism.32Lasda Parker Co-precipitate vesicles: possible mechanism clearance.PLoS One. e0148407https://doi.org/10.1371/journal.pone.0148407Crossref (260) highly EV-packed partially cancers; (exo-circRNAs) considered primarily biomarkers screening early onset.32Lasda Scholar,33Du W.W. Fang Dhaliwal Yang Yee B.B. Promotion tumor progression transmission circSKA3.Mol. Ther. Nucleic Acids. 27: 276-292https://doi.org/10.1016/j.omtn.2021.11.027Abstract (7) due increased stability, support translation typical mRNA.34Wesselhoeft R.A. Kowalski P.S. Anderson D.G. potent 2629https://doi.org/10.1038/s41467-018-05096-6Crossref (240) internal ribosome entry site (IRES) interest.34Wesselhoeft persist one approach generating enhanced long-term expression. Such application would especially useful treatments extend exposure antigens or, generally, out dose. occurring open reading frame (ORF)-possessing minority yet capable translation, coding capacity.35Miao Ni Coding circRNAs: discoveries challenges.PeerJ. e10718https://doi.org/10.7717/peerj.10718Crossref Wesselhoeft achieved robust luciferase, EGFP, erythropoietin, CRISPR-associated endonuclease 9 (Cas9) transfection self-splicing intron-induced HEK293 cells.34Wesselhoeft Qu created severe acute respiratory syndrome coronavirus (SARS-CoV-2) spike performed experiments mice test immunization capacity encapsulated LNPs.36Qu Yi Zhang Tian al.Circular against variants.Cell. 185: 1728-1744.e16https://doi.org/10.1016/j.cell.2022.03.044Abstract Mice treated antibodies T responses similar those counterparts mRNA.36Qu Overall, results suggest make mRNAs improve general efficacy therapies treating infectious Ideally, code long-lasting allows developed means unbound CRY2 plant changes conformation blue light, CIBN truncated version CIB1, affinity its excited form.37Kennedy Hughes Peteya L.A. Schwartz J.W. Ehlers Tucker C.L. Rapid blue-light-mediated induction living Methods. 2010; 7: 973-975https://doi.org/10.1038/nmeth.1524Crossref (749) CIB1 attached cytosolic tail marker CD9 reporter mCherry GFP.38Yim Ryu S.W. Choi Lee Kim Shaker M.R. Sun Park al.Exosome engineering intracellular soluble optically reversible protein-protein module.Nat. 12277https://doi.org/10.1038/ncomms12277Crossref (318) named EXPLOR, cargo-CRY2 when exposed light. absence complex freely available Using approach, successfully Cre recombinase nuclear κB (NF-κB) suppressor srIκB EVs.39Choi Mirzaaghasi Heo Y.N. Shin Cho E.S. Song Chung Yook Yoo T.H. Exosome-based super-repressor IkappaBalpha relieves sepsis-associated organ damage mortality.Sci. Adv. eaaz6980https://doi.org/10.1126/sciadv.aaz6980Crossref (72) Based model, Osteikoetxea tested whether Cas9 systems heterodimerization activating stimulus.40Osteikoetxea Silva Lázaro-Ibáñez Salmond Shatnyeva Stein Schick Wren Lindgren Firth al.Engineered editing tool.J. e12225https://doi.org/10.1002/jev2.12225Crossref (5) PHIB PIF6, 630 nm molecule phycocyanobilin, VVD nanomagnets finally FKBP FRB, rapamycin. group CRY2-CIB1 resulted highest fractions, 20 per EV.40Osteikoetxea noteworthy observation study data MysPalm advantageous tetraspanin markers CD9. Two possib
Язык: Английский
Процитировано
104
Translational Oncology, Год журнала: 2024, Номер 50, С. 102121 - 102121
Опубликована: Сен. 14, 2024
Язык: Английский
Процитировано
61
Biochemistry and Biophysics Reports, Год журнала: 2024, Номер 37, С. 101644 - 101644
Опубликована: Янв. 17, 2024
Exosomes are a type of extracellular vesicle that contains bioactive molecules can be secreted by most cells. Nevertheless, the content these cells differs depending on cell from which they originate. The exosome plays crucial role in modulating intercellular communication conveying molecular messages to neighboring or distant Cancer-derived exosomes transfer several types into tumor microenvironment, including high levels microRNA (miRNA). These miRNAs significantly affect proliferation, angiogenesis, apoptosis resistance, metastasis, and immune evasion. Increasing evidence indicates exosomal (exomiRs) regulating cancer resistance apoptosis. In cells, exomiRs orchestrate channels between them their surrounding gene expression controlling signaling pathways. This review presents an outline present-day knowledge mechanisms target drive Also, our study looks at regulatory mediating microenvironmental specifically stromal evade therapy-induced
Язык: Английский
Процитировано
20
International Journal of Nanomedicine, Год журнала: 2021, Номер Volume 16, С. 2803 - 2818
Опубликована: Апрель 1, 2021
Background: Circular RNAs (circRNAs) have been identified as key factors in the development of hepatocellular carcinoma (HCC). However, role and potential molecular mechanism circRNAs HCC remain largely unclear. In addition, exosomes are known important messengers cross-talk between tumor cells immune cells, while extracellular cell-to-cell communication remains not Methods: The level hsa_circ_0074854 cell lines cell-derived was assessed using RT-qPCR assay. CCK-8 transwell assays were used to determine viability, migration invasion cells. Results: Hsa_circ_0074854 expression upregulated tissues lines. Additionally, knockdown found inhibit growth vitro vivo. Mechanistically, inhibited via interacting with human antigen R (HuR) reduce its stability. Furthermore, can be transferred from macrophages exosomes. Exosomes downregulated suppressed macrophage M2 polarization, which turn suppressing both Conclusion: Downregulation suppresses HuR exosomes-mediated polarization. Collectively, these findings may help understand diagnosis treatment HCC. Keywords: circular RNAs, carcinoma, exosomes,
Язык: Английский
Процитировано
88
Biosensors and Bioelectronics X, Год журнала: 2022, Номер 12, С. 100269 - 100269
Опубликована: Окт. 21, 2022
A biomarker is an indicator for sensing the human state of health. There has been a wide-scale investigation into using portable analytical platforms real-time monitoring biomarkers. Biomolecular recognition, manufacturing simplification technologies, integration microfluidics and optics, developed approaches to biosensor device have quickly moved optical-based sensors point use in laboratory. Biosensors are tools incorporating biorecognition element. Optical technology essential modern biomedical applications as they provide quick powerful ways detect distinguish target analytes from diversity samples. Optical-based biosensors extra advantages such high sensitivity, reliability, robustness, potential be combined on sole chip. Recently, extensively investigated detection diversified biomarkers label-free mode or by binding recognition material molecules concern. This critical review article focuses current progress techniques including surface plasmon resonance (SPR) surface-enhanced Raman scattering (SERS), fluorescence (SEF), whispering gallery (WGM), photonic crystals (PCs) opals plasmonic nanoparticles enhance sensitivity significant As result, we overview latest advancement growing optical virus, bacteria, protein, cell, cancer detection. The requirement future perspective also addressed.
Язык: Английский
Процитировано
49
Microchimica Acta, Год журнала: 2025, Номер 192(4)
Опубликована: Март 5, 2025
The review article provides a short introduction to exosomes with the focus use as disease markers itself (i.e. their concentration or presence of some specific receptors) source biomarkers such proteins and metabolites. In detail, we are discussing various methods exosome isolation main paper is on affinity capture exosomes, since them can be applied sub-populations produced by organs. comprehensive overview magnetic (bio)affinity detection exosomal cargo using different ligands antibodies, DNA aptamers, peptides, glycan-based recognition, transferrin-based approaches, based recognition phospholipids other approaches including electrostatic interactions. in detail key analytical clinical parameters form an extensive table summarising outcomes published last two years (2023-2024). Finally, also conclusions sections pros cons for and/or determination content.
Язык: Английский
Процитировано
2
Nanoscale, Год журнала: 2021, Номер 13(13), С. 6661 - 6677
Опубликована: Янв. 1, 2021
3D-AFM showed the presence of distinct nanodomains bulging out from membrane surface, which can be attributed to membrane-associated proteins.
Язык: Английский
Процитировано
53
Cancers, Год журнала: 2022, Номер 14(4), С. 1090 - 1090
Опубликована: Фев. 21, 2022
Cancer chemotherapy may induce a multidrug resistance (MDR) phenotype. The development of MDR is based on various molecular causes, which the following are very common: induction ABC transporter expression; induction/activation drug-metabolizing enzymes; alteration expression/function apoptosis-related proteins; changes in cell cycle checkpoints; elevated DNA repair mechanisms. Although these mechanisms well described, information their interaction overall still lacking. MicroRNA (miRNA) expression and subsequent RNA interference candidates that could be important players interplay regulation post-transcriptional processes proteosynthetic pathway considered to major function miRNAs. Due complementarity, they able bind target mRNAs, prevents mRNAs from interacting effectively with ribosome, degradation can occur. aim this paper provide an overview possible role miRNAs lead MDR. possibility considering as either specific effectors or interesting targets for cancer therapy also analyzed.
Язык: Английский
Процитировано
38