[1] E. L. Andaloussi, S. I. Mager, X. O. Breakefield, M. J. Wood, "Extracellular vesicles: Biology and emerging therapeutic opportunities," Nat. Rev. Drug Discov. 12, 347–357 (2013).
[2] C. Thery, S. Amigorena, G. Raposo, A. Clayton, "Isolation and characterization of exosomes from cell culture supernatants and biological fluids," Curr. Protoc. Cell Biol. Chapter 3, Unit 3.22 (2006).
[3] J. C. Akers, D. Gonda, R. Kim, B. S. Carter, C. C. Chen, "Biogenesis of extracellular vesicles (EV): Exosomes, microvesicles, retrovirus-like vesicles, and apoptotic bodies," J. Neurooncol. 113, 1–11 (2013).
[4] C. Thery et al., "Minimal information for studies of extracellular vesicles 2018 (MISEV2018): A position statement of the international society for extracellular vesicles and update of the MISEV2014 guidelines," J. Extracell Vesicles. 7, 1535750 (2018).
[5] R. M. Johnstone, M. Adam, J. R. Hammond, L. Orr, C. Turbide, "Vesicle formation during reticulocyte maturation. Association of plasma membrane activities with released vesicles (exosomes)," J. Biol Chem. 262, 9412–9420 (1987).
[6] H. Valadi et al., "Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells," Nat. Cell Biol. 9, 654–659 (2007).
[7] M. Tkach, C. Thery, "Communication by extracellular vesicles: Where we are and where we need to go," Cell 164, 1226–1232 (2016).
[8] H. Liu, X. Sun, X. Gong, G. Wang, "Human umbilical cord mesenchymal stem cells derived exosomes exert antiapoptosis effect via activating PI3K/Akt/mTOR pathway on H9C2 cells," J. Cell Biochem. 120, 14455–14464 (2019).
[9] J. Zheng et al., "Extracellular vesicles derived from human umbilical cord mesenchymal stem cells protect liver ischemia/reperfusion injury by reducing CD154 expression on CD4+ T cells via CCT2," Adv. Sci. (Weinh) 7, 1903746 (2020).
[10] M. Mathieu, L. Martin-Jaular, G. Lavieu, C. Thery, "Specificities of secretion and uptake of exosomes and other extracellular vesicles for cell-to-cell communication," Nat. Cell Biol. 21, 9–17 (2019).
[11] S. Keshtkar, N. Azarpira, M. H. Ghahremani, "Mesenchymal stem cell-derived extracellular vesicles: Novel frontiers in regenerative medicine," Stem Cell. Res. Ther. 9, 63 (2018).
[12] S. Koniusz et al., "Extracellular vesicles in physiology, pathology, and therapy of the immune and central nervous system, with focus on extracellular vesicles derived from mesenchymal stem cells as therapeutic tools," Front. Cell. Neurosci. 10, 109 (2016).
[13] L. V. K. Reddy, D. Murugan, M. Mullick, E. T. Begum Moghal, D. Sen, "Recent approaches for angiogenesis in search of successful tissue engineering and regeneration," Curr. Stem Cell Res. Ther. 15, 111–134 (2020).
[14] S. Zhang et al., "MSC exosomes mediate cartilage repair by enhancing proliferation, attenuating apoptosis and modulating immune reactivity," Biomaterials 156, 16–27 (2018).
[15] G. R. Willis et al., "Mesenchymal stromal cell exosomes ameliorate experimental bronchopulmonary dysplasia and restore lung function through macrophage immunomodulation," Am. J. Respir. Crit. Care Med. 197, 104–116 (2018).
[16] G. Qiu et al., "Mesenchymal stem cell-derived extracellular vesicles affect disease outcomes via transfer of microRNAs," Stem Cell. Res. Ther. 9, 320 (2018).
[17] J. Yao et al., "Extracellular vesicles derived from human umbilical cord mesenchymal stem cells alleviate rat hepatic ischemia-reperfusion injury by suppressing oxidative stress and neutrophil inflammatory response," FASEB J. 33, 1695–1710 (2019).
[18] W. Jiang et al., "Human umbilical cord MSC-derived exosomes suppress the development of CCl4- induced liver injury through antioxidant effect," Stem Cells Int. 2018, 6079642 (2018).
[19] K. Xie, L. Liu, J. Chen, F. Liu, "Exosomes derived from human umbilical cord blood mesenchymal stem cells improve hepatic ischemia reperfusion injury via delivering miR-1246," Cell Cycle 18, 3491– 3501 (2019).
[20] A. Ciullo et al., "Exosomal expression of CXCR4 targets cardioprotective vesicles to myocardial infarction and improves outcome after systemic administration," Int. J. Mol. Sci. 20, 468 (2019).
[21] S. Fujii et al., "Graft-Versus-Host disease amelioration by human bone marrow mesenchymal stromal/ stem cell-derived extracellular vesicles is associated with peripheral preservation of naive T cell populations," Stem Cells 36, 434–445 (2018).
[22] L. Kordelas et al., "MSC-derived exosomes: A novel tool to treat therapy-refractory graft-versus-host disease," Leukemia 28, 970–973 (2014).
[23] H. Cao et al., "In vivo tracking of mesenchymal stem cell-derived extracellular vesicles improving mitochondrial function in renal ischemia-reperfusion injury," ACS Nano 14, 4014–4026 (2020).
[24] Y. Chen, K. Xue, X. Zhang, Z. Zheng, K. Liu, "Exosomes derived from mature chondrocytes facilitate subcutaneous stable ectopic chondrogenesis of cartilage progenitor cells," Stem Cell. Res. Ther. 9, 318 (2018).
[25] B. You, W. Xu, B. Zhang, "Engineering exosomes: a new direction for anticancer treatment," Am. J. Cancer Res. 8, 1332–1342 (2018).
[26] A. Thakur et al., "Inhibition of glioma cells' proliferation by doxorubicin-loaded exosomes via micro- fluidics," Int. J. Nanomed. 15, 8331–8343 (2020).
[27] S. K. Limoni, M. F. Moghadam, S. M. Moazzeni, H. Gomari, F. Salimi, "Engineered exosomes for targeted transfer of siRNA to HER2 positive breast cancer cells," Appl. Biochem. Biotechnol. 187, 352– 364 (2019).
[28] S. T. Chuo, J. C. Chien, C. P. Lai, "Imaging extracellular vesicles: Current and emerging methods," J. Biomed. Sci. 25, 91 (2018).
[29] V. Hyenne, O. Lefebvre, J. G. Goetz, "Going live with tumor exosomes and microvesicles," Cell Adh. Migr. 11, 173–186 (2017).
[30] Y.-J. Li, J.-Y. Wu, J.-M. Wang, X.-B. Hu, D.-X. Xiang, "Emerging strategies for labeling and tracking of extracellular vesicles," J. Controlled Release 328, 141–159 (2020).
[31] O. Betzer et al., "Advances in imaging strategies for in vivo tracking of exosomes," Wiley Interdiscip. Rev. Nanomed. Nanobiotechnol. 12, e1594 (2019).
[32] O. P. Wiklander et al., "Extracellular vesiclein vivo biodistribution is determined by cell source, route of administration and targeting," J. Extracell. Vesicles 4, 26316 (2015).
[33] S. Wen et al., "Biodistribution of mesenchymal stem cell-derived extracellular vesicles in a radiation injury bone marrow murine model," Int. J. Mol. Sci. 20, 5468 (2019).
[34] S. W. Wen et al., "The Biodistribution and immune suppressive effects of breast cancer-derived exosomes," Cancer Res. 76, 6816–6827 (2016).
[35] M. Mendt et al., "Generation and testing of clinicalgrade exosomes for pancreatic cancer," JCI Insight 3, e99263 (2018).
[36] R.Tamura,S.Uemoto,Y.Tabata,"Immunosuppressive effect of mesenchymal stem cell-derived exosomes on a concanavalin A-induced liver injury model," Inflamm. Regen. 36, 26 (2016).
[37] R. Tamura, S. Uemoto, Y. Tabata, "Augmented liver targeting of exosomes by surface modification with cationized pullulan," Acta Biomater. 57, 274– 284 (2017).
[38] A. E. Russell et al., "Biological membranes in EV biogenesis, stability, uptake, and cargo transfer: An ISEV position paper arising from the ISEV membranes and EVs workshop," J. Extracell. Vesicles 8, 1684862 (2019).
[39] P. Zhang et al., "In vivo tracking of multiple tumor exosomes labeled by phospholipid-based bioorthogonal conjugation," Anal. Chem. 90, 11273–11279 (2018).
[40] S. M. Kim et al., "Cancer-derived exosomes as a delivery platform of CRISPR/Cas9 confer cancer cell tropism-dependent targeting," J. Control. Release 266, 8–16 (2017).
[41] Z. Yang et al., "Functional exosome-mimic for delivery of siRNA to cancer: In vitro and in vivo evaluation," J. Control. Release 243, 160–171 (2016).
[42] H. Cao et al., "In vivo real-time imaging of extracellular vesicles in liver regeneration via aggregation- induced emission luminogens," ACS Nano 13, 3522–3533 (2019).
[43] A. Zomer et al., "In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior," Cell 161, 1046–1057 (2015).
[44] A. Suetsugu et al., "Imaging exosome transfer from breast cancer cells to stroma at metastatic sites in orthotopic nude-mouse models," Adv. Drug Deliv. Rev. 65, 383–390 (2013).
[45] C. P. Lai et al., "Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters," Nat. Commun. 6, 7029 (2015).
[46] S. Manca et al., "Milk exosomes are bioavailable and distinct microRNA cargos have unique tissue distribution patterns," Sci. Rep. 8, 11321 (2018).
[47] C. E. Badr, B. A. Tannous, "Bioluminescence imaging: Progress and applications," Trends Biotechnol. 29, 624–633 (2011).
[48] Y. Takahashi et al., "Visualization and in vivo tracking of the exosomes of murine melanoma B16- BL6 cells in mice after intravenous injection," J. Biotechnol. 165, 77–84 (2013).
[49] T. Imai et al., "Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice," J. Extracell. Vesicles 4, 26238 (2015).
[50] C. Charoenviriyakul et al., "Cell type-specific and common characteristics of exosomes derived from mouse cell lines: Yield, physicochemical properties, and pharmacokinetics," Eur. J. Pharm. Sci. 96, 316–322 (2017).
[51] K. Zhang et al., "Enhanced therapeutic effects of mesenchymal stem cell-derived exosomes with an injectable hydrogel for hindlimb ischemia treatment," ACS Appl. Mater. Interf. 10, 30081– 30091 (2018).
[52] C. P. Lai et al., "Dynamic biodistribution of extracellular vesicles in vivo using a multimodal imaging reporter," ACS Nano 8, 483–494 (2014).
[53] K. E. van der Vos et al., "Directly visualized glioblastoma- derived extracellular vesicles transfer RNA to microglia/macrophages in the brain," Neuro-Oncol. 18, 58–69 (2016).
[54] T. Hikita, M. Miyata, R. Watanabe, C. Oneyama, "Sensitive and rapid quantification of exosomes by fusing luciferase to exosome marker proteins," Sci. Rep. 8, 14035 (2018).
[55] P. Gangadaran et al., "A new bioluminescent reporter system to study the biodistribution of systematically injected tumor-derived bioluminescent extracellular vesicles in mice," Oncotarget 8, 109894–109914 (2017).
[56] B. C. Ahn, "Requisites for successful theranostics with radionuclide-based reporter gene imaging," J. Drug Target. 22, 295–303 (2014).
[57] M. H. Rashid et al., "Differential in vivo biodistribution of 131I-labeled exosomes from diverse cellular origins and its implication for theranostic application," Nanomedicine 21, 102072 (2019).
[58] M. Morishita et al., "Quantitative analysis of tissue distribution of the B16BL6-derived exosomes using a streptavidin–lactadherin fusion protein and iodine- 125-labeled biotin derivative after intravenous injection in mice," J. Pharm. Sci. 104, 705–713 (2015).
[59] T. Smyth et al., "Biodistribution and delivery effi- ciency of unmodified tumor-derived exosomes," J. Control. Release. 199, 145–155 (2015).
[60] F. N. Faruqu et al., "Membrane radiolabelling of exosomes for comparative biodistribution analysis in immunocompetent and immunodeficient mice — A novel and universal approach," Theranostics 9, 1666–1682 (2019).
[61] D. W. Hwang et al., "Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO," Sci. Rep. 5, 15636 (2015).
[62] Z. Varga et al., "Radiolabeling of extracellular vesicles with 99mTc for quantitative in vivo imaging studies," Cancer Biother. Radiopharm. 31, 168–173 (2016).
[63] P. Gangadaran et al., "In vivo non-invasive imaging of radio-labeled exosome-mimetics derived from red blood cells in mice," Front. Pharmacol. 9, 817 (2018).
[64] M. I. Gonzalez, P. Martin-Duque, M. Desco, B. Salinas, "Radioactive labeling of milk-derived exosomes with 99mTc and in vivo tracking by SPECT imaging," Nanomaterials (Basel) 10, 1062 (2020).
[65] S. Molavipordanjani et al., "99mTc-radiolabeled HER2 targeted exosome for tumor imaging," Eur. J. Pharm. Sci. 148, 105312 (2020).
[66] S. Shi et al., "Copper-64 labeled PEGylated exosomes for in vivo positron emission tomography and enhanced tumor retention," Bioconjug. Chem. 30, 2675–2683 (2019).
[67] K. O. Jung et al., "Identification of lymphatic and hematogenous routes of rapidly labeled radioactive and fluorescent exosomes through highly sensitive multimodal imaging," Int. J. Mol. Sci. 21, 7850 (2020).
[68] F. Royo, U. Cossio, A. Ruiz de Angulo, J. Llop, J. M. Falcon-Perez, "Modification of the glycosylation of extracellular vesicles alters their biodistribution in mice," Nanoscale 11, 1531–1537 (2019).
[69] O. Betzer et al., "In vivo neuroimaging of exosomes using gold nanoparticles," ACS Nano 11, 10883– 10893 (2017).
[70] S. Guo et al., "Intranasal delivery of mesenchymal stem cell derived exosomes loaded with phosphatase and tensin homolog siRNA repairs complete spinal cord injury," ACS Nano 13, 10015–10028 (2019).
[71] N. Perets et al., "Golden exosomes selectively target brain pathologies in neurodegenerative and neurodevelopmental disorders," Nano Lett. 19, 3422–3431 (2019).
[72] P. Lara et al., "Gold nanoparticle based doublelabeling of melanoma extracellular vesicles to determine the specificity of uptake by cells and preferential accumulation in small metastatic lung tumors," J. Nanobiotechnol. 18, 20 (2020).
[73] L. Hu, S. A. Wickline, J. L. Hood, "Magnetic resonance imaging of melanoma exosomes in lymph nodes," Magn. Reson. Med. 74, 266–271 (2015).
[74] K. O. Jung, H. Jo, J. H. Yu, S. S. Gambhir, G. Pratx, "Development and MPI tracking of novel hypoxia-targeted theranostic exosomes," Biomaterials 177, 139–148 (2018).
[75] A. Busato et al., "Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: A new method to obtain labeled exosomes," Int. J. Nanomed. 11, 2481–2490 (2016).
[76] A. Busato et al., "Labeling and magnetic resonance imaging of exosomes isolated from adipose stem cells," Curr. Protoc. Cell Biol. 75, 3. 44. 1–3. 44. 15 (2017).
[77] J. Abello, T. D. T. Nguyen, R. Marasini, S. Aryal, M. L. Weiss, "Biodistribution of gadolinium- and near infrared-labeled human umbilical cord mesenchymal stromal cell-derived exosomes in tumor bearing mice," Theranostics 9, 2325–2345 (2019).
[78] R. J. C. Bose et al., "Tumor cell-derived extracellular vesicle-coated nanocarriers: An efficient theranostic platform for the cancer-specific delivery of anti-miR-21 and imaging agents," ACS Nano 12, 10817–10832 (2018).
[79] T. Liu, Y. Zhu, R. Zhao, X. Wei, X. Xin, "Visualization of exosomes from mesenchymal stem cells in vivo by magnetic resonance imaging," Magn. Reson. Imag. 68, 75–82 (2020).
[80] C. Kim, C. Favazza, L. V. Wang, "In vivo photoacoustic tomography of chemicals: High-resolution functional and molecular optical imaging at new depths," Chem. Rev. 110, 2756–2782 (2010).
[81] Q. Chen et al., "A self-assembled albumin-based nanoprobe for in vivo ratiometric photoacoustic pH imaging," Adv. Mater. 27, 6820–6827 (2015).
[82] Y. Li, Y. Chen, M. Du, Z.-Y. Chen, "Ultrasound technology for molecular imaging: From contrast agents to multimodal imaging," ACS Biomater Sci. Eng. 4, 2716–2728 (2018).
[83] Q. Chen et al., "H2 O2-responsive liposomal nanoprobe for photoacoustic inflammation imaging and tumor theranostics via in vivo chromogenic assay," Proc. Natl. Acad. Sci/USA. 114, 5343–5348 (2017).
[84] Y. J. Piao et al., "Breast cancer cell-derived exosomes and macrophage polarization are associated with lymph node metastasis," Oncotarget 9, 7398– 7410 (2018).
[85] H. Ding et al., "Exosome-like nanozyme vesicles for H2O2-responsive catalytic photoacoustic imaging of xenograft nasopharyngeal carcinoma," Nano Lett. 19, 203–209 (2019).
[86] Y. Jang et al., "Exosome-based photoacoustic imaging guided photodynamic and immunotherapy for the treatment of pancreatic cancer," J. Control. Release. 330, 293–304 (2020).
[87] D. Zhu et al., "Stellate plasmonic exosomes for penetrative targeting tumor NIR-II thermo-radiotherapy," ACS Appl. Mater. Interfaces 12, 36928– 36937 (2020).
[88] J. Y. Zhao et al., "Ultrasmall magnetically engineered Ag2Se quantum dots for instant efficient labeling and whole-body high-resolution multimodal real-time tracking of cell-derived microvesicles," J. Am. Chem. Soc. 138, 1893–1903 (2016).
[89] Y. Cao et al., "Engineered exosome-mediated nearinfrared- II region V2C quantum dot delivery for nucleus-target low-temperature photothermal therapy," ACS Nano 13, 1499–1510 (2019).
[90] S. Shaikh et al., "Real-time multimodal bioimaging of cancer cells and exosomes through biosynthesized iridium and iron nanoclusters," ACS Appl. Mater. Interfaces. 10, 26056–26063 (2018).
