Skip to main content
SpringerLink
Log in
Book cover

Radionanomedicine pp 167–182Cite as

Endogenous Radionanomedicine: Validation of Therapeutic Potential

  • Chapter
  • First Online:

Part of the book series: Biological and Medical Physics, Biomedical Engineering ((BIOMEDICAL))

Abstract

Exosomes have features to be able to promise therapeutic opportunities, which are exosomes-mediated pathogenesis in certain diseases, and thus their inherent therapeutic potential, and again possibility of use of exosomes as drug carriers. There have been increasing interests in this therapeutic potential of exosomes owing to the recent reports in regenerative medicine, tumor management, infection, and organ transplantation. Radionanomedicines i.e. radiolabeled exosomes provide advantages of non-invasive, less toxic, highly penetrable, highly sensitive, and quantification-enabling characteristic of radioactivity for validation of therapeutic potentials of exosomes. Radiolabeled exosomes are expected to allow their theranostic use even in clinical settings. However, there remain the issues to overcome the low yields of exosomes, release of free radioisotope after degradation of exosomes, and yet unveiled dosimetry of therapeutic radiolabeled exosomes. This chapter reviews current evidences of therapeutic applications of exosomes in regenerative medicine and tumor management and discusses radiolabeled exosomes or exosome-mimetic nanovesicles as well as remaining issues in endogenous radionanomedicines regarding the desired therapeutic potentials of radiolabeled or unlabeled exosomes.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   159.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

References

  1. S.E. Andaloussi, I. Mäger, X.O. Breakefield, M.J. Wood, Extracellular vesicles: biology and emerging therapeutic opportunities. Nat. Rev. Drug Discov. 12(5), 347–357 (2013)

    Article  Google Scholar 

  2. A.M. Merino, M.J. Hoogduijn, F.E. Borras, M. Franquesa, Therapeutic potential of extracellular vesicles. Front. Immunol. 5, 658 (2014)

    Article  Google Scholar 

  3. H. Choi, D.S. Lee, Illuminating the physiology of extracellular vesicles. Stem Cell Res. Ther. 7(1), 55 (2016)

    Article  Google Scholar 

  4. J.L. Hood, R.S. San, S.A. Wickline, Exosomes released by melanoma cells prepare sentinel lymph nodes for tumor metastasis. Cancer Res. 71(11), 3792–3801 (2011)

    Article  Google Scholar 

  5. Ohno S-i, M. Takanashi, K. Sudo, S. Ueda, A. Ishikawa, N. Matsuyama et al., Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol. Ther. 21(1), 185–191 (2013)

    Article  Google Scholar 

  6. H.C. Christianson, K.J. Svensson, T.H. van Kuppevelt, J.-P. Li, M. Belting, Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc. Natl. Acad. Sci. U S A. 110(43), 17380–17385 (2013)

    Article  ADS  Google Scholar 

  7. T. Tian, Y.L. Zhu, F.H. Hu, Y.Y. Wang, N.P. Huang, Z.D. Xiao, Dynamics of exosome internalization and trafficking. J. Cell. Physiol. 228(7), 1487–1495 (2013)

    Article  Google Scholar 

  8. H. De La Peña, J. Madrigal, S. Rusakiewicz, M. Bencsik, G.W. Cave, A. Selman et al., Artificial exosomes as tools for basic and clinical immunology. J. Immunol. Methods 344(2), 121–132 (2009)

    Article  Google Scholar 

  9. L. Hu, S.A. Wickline, J.L. Hood, Magnetic resonance imaging of melanoma exosomes in lymph nodes. Magn. Reson. Med. 74(1), 266–271 (2015)

    Article  Google Scholar 

  10. T. Smyth, M. Kullberg, N. Malik, P. Smith-Jones, M.W. Graner, T.J. Anchordoquy, Biodistribution and delivery efficiency of unmodified tumor-derived exosomes. J. Control Release. 199, 145–155 (2015)

    Article  Google Scholar 

  11. H. Choi, S.C. Jang, M.Y. Yoo, J.Y. Park, N.E. Choi, H.J. Oh et al., Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using 99mTc-HMPAO. Sci. Rep. 5, 15636 (2015)

    Article  ADS  Google Scholar 

  12. M. Morishita, Y. Takahashi, M. Nishikawa, K. Sano, K. Kato, T. Yamashita 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(2), 705–713 (2015)

    Article  Google Scholar 

  13. Z. Varga, I. Gyurkó, K. Pálóczi, E.I. Buzás, I. Horváth, N. Hegedűs et al., Radiolabeling of extracellular vesicles with 99mTc for quantitative in vivo imaging studies. Cancer Biother. Radiopharm. 31(5), 168–173 (2016)

    Article  Google Scholar 

  14. O.G. De Jong, B.W. Van Balkom, R.M. Schiffelers, C.V. Bouten, M.C. Verhaar, Extracellular vesicles: potential roles in regenerative medicine. Front. Immunol. 5, 608 (2014)

    Google Scholar 

  15. H. Xin, Y. Li, Z. Liu, X. Wang, X. Shang, Y. Cui et al., MiR-133b promotes neural plasticity and functional recovery after treatment of stroke with multipotent mesenchymal stromal cells in rats via transfer of exosome-enriched extracellular particles. Stem Cells 31(12), 2737–2746 (2013)

    Article  Google Scholar 

  16. M.A. Lopez-Verrilli, F. Picou, F.A. Court, Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system. Glia 61(11), 1795–1806 (2013)

    Article  Google Scholar 

  17. A.D. Pusic, K.M. Pusic, B.L. Clayton, R.P. Kraig, IFNγ-stimulated dendritic cell exosomes as a potential therapeutic for remyelination. J. Neuroimmunol. 266(1), 12–23 (2014)

    Article  Google Scholar 

  18. K. Yuyama, H. Sun, S. Sakai, S. Mitsutake, M. Okada, H. Tahara et al., Decreased amyloid-β pathologies by intracerebral loading of glycosphingolipid-enriched exosomes in Alzheimer model mice. J. Biol. Chem. 289(35), 24488–24498 (2014)

    Article  Google Scholar 

  19. R.C. Lai, F. Arslan, M.M. Lee, N.S.K. Sze, A. Choo, T.S. Chen et al., Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 4(3), 214–222 (2010)

    Article  Google Scholar 

  20. F. Arslan, R.C. Lai, M.B. Smeets, L. Akeroyd, A. Choo, E.N. Aguor et al., Mesenchymal stem cell-derived exosomes increase ATP levels, decrease oxidative stress and activate PI3K/Akt pathway to enhance myocardial viability and prevent adverse remodeling after myocardial ischemia/reperfusion injury. Stem Cell Res. 10(3), 301–312 (2013)

    Article  Google Scholar 

  21. R.C. Lai, R.W.Y. Yeo, K.H. Tan, S.K. Lim, Mesenchymal stem cell exosome ameliorates reperfusion injury through proteomic complementation. Regen. Med. 8(2), 197–209 (2013)

    Article  Google Scholar 

  22. L. Chen, Y. Wang, Y. Pan, L. Zhang, C. Shen, G. Qin et al., Cardiac progenitor-derived exosomes protect ischemic myocardium from acute ischemia/reperfusion injury. Biochem. Biophys. Res. Commun. 431(3), 566–571 (2013)

    Article  Google Scholar 

  23. L. Barile, V. Lionetti, E. Cervio, M. Matteucci, M. Gherghiceanu, L.M. Popescu et al., Extracellular vesicles from human cardiac progenitor cells inhibit cardiomyocyte apoptosis and improve cardiac function after myocardial infarction. Cardiovasc. Res. 103(4), 530–541 (2014)

    Article  Google Scholar 

  24. J.M. Vicencio, D.M. Yellon, V. Sivaraman, D. Das, C. Boi-Doku, S. Arjun et al., Plasma exosomes protect the myocardium from ischemia-reperfusion injury. J. Am. Coll. Cardiol. 65(15), 1525–1536 (2015)

    Article  Google Scholar 

  25. H. Zhang, M. Xiang, D. Meng, N. Sun, S. Chen, Inhibition of myocardial ischemia/reperfusion injury by exosomes secreted from mesenchymal stem cells. Stem Cells Int. 2016, 8 (2016)

    Google Scholar 

  26. H. Gomez, C. Ince, D. De Backer, P. Pickkers, D. Payen, J. Hotchkiss et al., A unified theory of sepsis-induced acute kidney injury: inflammation, microcirculatory dysfunction, bioenergetics and the tubular cell adaptation to injury. Shock 41(1), 3 (2014)

    Article  Google Scholar 

  27. M. Morigi, B. Imberti, C. Zoja, D. Corna, S. Tomasoni, M. Abbate et al., Mesenchymal stem cells are renotropic, helping to repair the kidney and improve function in acute renal failure. J. Am. Soc. Nephrol. 15(7), 1794–1804 (2004)

    Article  Google Scholar 

  28. M. Morigi, M. Introna, B. Imberti, D. Corna, M. Abbate, C. Rota et al., Human bone marrow mesenchymal stem cells accelerate recovery of acute renal injury and prolong survival in mice. Stem Cells 26(8), 2075–2082 (2008)

    Article  Google Scholar 

  29. F. Tögel, K. Weiss, Y. Yang, Z. Hu, P. Zhang, C. Westenfelder, Vasculotropic, paracrine actions of infused mesenchymal stem cells are important to the recovery from acute kidney injury. Am. J. Physiol. Renal. Physiol. 292(5), F1626–F1635 (2007)

    Article  Google Scholar 

  30. B. Bi, R. Schmitt, M. Israilova, H. Nishio, L.G. Cantley, Stromal cells protect against acute tubular injury via an endocrine effect. J. Am. Soc. Nephrol. 18(9), 2486–2496 (2007)

    Article  Google Scholar 

  31. B. Imberti, M. Morigi, S. Tomasoni, C. Rota, D. Corna, L. Longaretti et al., Insulin-like growth factor-1 sustains stem cell–mediated renal repair. J. Am. Soc. Nephrol. 18(11), 2921–2928 (2007)

    Article  Google Scholar 

  32. V. Cantaluppi, L. Biancone, G.M. Romanazzi, F. Figliolini, S. Beltramo, F. Galimi et al., Macrophage stimulating protein may promote tubular regeneration after acute injury. J. Am. Soc. Nephrol. 19(10), 1904–1918 (2008)

    Article  Google Scholar 

  33. A. Ranghino, S. Bruno, B. Bussolati, A. Moggio, V. Dimuccio, M. Tapparo et al., The effects of glomerular and tubular renal progenitors and derived extracellular vesicles on recovery from acute kidney injury. Stem Cell Res. Ther. 8(1), 24 (2017)

    Article  Google Scholar 

  34. S. Bruno, C. Grange, M.C. Deregibus, R.A. Calogero, S. Saviozzi, F. Collino et al., Mesenchymal stem cell-derived microvesicles protect against acute tubular injury. J. Am. Soc. Nephrol. 20(5), 1053–1067 (2009)

    Article  Google Scholar 

  35. S. Gatti, S. Bruno, M.C. Deregibus, A. Sordi, V. Cantaluppi, C. Tetta et al., Microvesicles derived from human adult mesenchymal stem cells protect against ischaemia–reperfusion-induced acute and chronic kidney injury. Nephrol. Dial. Transplant. 26, 1474–1483 (2011)

    Article  Google Scholar 

  36. Y. Zhou, H. Xu, W. Xu, B. Wang, H. Wu, Y. Tao et al., Exosomes released by human umbilical cord mesenchymal stem cells protect against cisplatin-induced renal oxidative stress and apoptosis in vivo and in vitro. Stem Cell Res. Ther. 4(2), 34 (2013)

    Article  Google Scholar 

  37. G. Zhang, D. Wang, S. Miao, X. Zou, G. Liu, Y. Zhu, Extracellular vesicles derived from mesenchymal stromal cells may possess increased therapeutic potential for acute kidney injury compared with conditioned medium in rodent models: A meta-analysis. Exp. Ther. Med. 11(4), 1519–1525 (2016)

    Article  Google Scholar 

  38. D. Burger, J.L. Viñas, S. Akbari, H. Dehak, W. Knoll, A. Gutsol et al., Human endothelial colony-forming cells protect against acute kidney injury: role of exosomes. Am. J. Pathol. 185(8), 2309–2323 (2015)

    Article  Google Scholar 

  39. J.L. Viñas, D. Burger, J. Zimpelmann, R. Haneef, W. Knoll, P. Campbell et al., Transfer of microRNA-486-5p from human endothelial colony forming cell–derived exosomes reduces ischemic kidney injury. Kidney Int. 90(6), 1238–1250 (2016)

    Article  Google Scholar 

  40. X. Zhang, X. Yuan, H. Shi, L. Wu, H. Qian, W. Xu, Exosomes in cancer: small particle, big player. J. Hematol. Oncol. 8(1), 83 (2015)

    Article  Google Scholar 

  41. T. Lener, M. Gimona, L. Aigner, V. Börger, E. Buzas, G. Camussi et al., Applying extracellular vesicles based therapeutics in clinical trials–an ISEV position paper. J. Extracell Vesicles 4(1), 30087 (2015)

    Article  Google Scholar 

  42. G. Raposo, H.W. Nijman, W. Stoorvogel, R. Liejendekker, C.V. Harding, C.J. Melief et al., B lymphocytes secrete antigen-presenting vesicles. J. Exp. Med. 183(3), 1161–1172 (1996)

    Article  Google Scholar 

  43. M.A. Morse, J. Garst, T. Osada, S. Khan, A. Hobeika, T.M. Clay et al., A phase I study of dexosome immunotherapy in patients with advanced non-small cell lung cancer. J. Transl. Med. 3(1), 1 (2005)

    Article  Google Scholar 

  44. B. Escudier, T. Dorval, N. Chaput, F. André, M.-P. Caby, S. Novault et al., Vaccination of metastatic melanoma patients with autologous dendritic cell (DC) derived-exosomes: results of the first phase I clinical trial. J. Transl. Med. 3(1), 1 (2005)

    Article  Google Scholar 

  45. B. Besse, M. Charrier, V. Lapierre, E. Dansin, O. Lantz, D. Planchard et al., Dendritic cell-derived exosomes as maintenance immunotherapy after first line chemotherapy in NSCLC. Oncoimmunology 5(4), e1071008 (2016)

    Article  Google Scholar 

  46. J. Wolfers, A. Lozier, G. Raposo, A. Regnault, C. Théry, C. Masurier et al., Tumor-derived exosomes are a source of shared tumor rejection antigens for CTL cross-priming. Nat. Med. 7(3), 297–303 (2001)

    Article  Google Scholar 

  47. E.J. Ekström, C. Bergenfelz, V. von Bülow, F. Serifler, E. Carlemalm, G. Jönsson et al., WNT5A induces release of exosomes containing pro-angiogenic and immunosuppressive factors from malignant melanoma cells. Mol. Cancer 13(1), 88 (2014)

    Article  Google Scholar 

  48. P. Altevogt, N.P. Bretz, J. Ridinger, J. Utikal, V. Umansky, Novel insights into exosome-induced, tumor-associated inflammation and immunomodulation. Semin Cancer Biol. 28, 51–57 (2014)

    Article  Google Scholar 

  49. M. Adams, H. Navabi, D. Croston, S. Coleman, Z. Tabi, A. Clayton et al., The rationale for combined chemo/immunotherapy using a Toll-like receptor 3 (TLR3) agonist and tumour-derived exosomes in advanced ovarian cancer. Vaccine 23(17), 2374–2378 (2005)

    Google Scholar 

  50. S. Dai, D. Wei, Z. Wu, X. Zhou, X. Wei, H. Huang et al., Phase I clinical trial of autologous ascites-derived exosomes combined with GM-CSF for colorectal cancer. Mol. Ther. 16(4), 782–790 (2008)

    Article  Google Scholar 

  51. L. Lugini, S. Cecchetti, V. Huber, F. Luciani, G. Macchia, F. Spadaro et al., Immune surveillance properties of human NK cell-derived exosomes. J. Immunol. 189(6), 2833–2842 (2012)

    Article  Google Scholar 

  52. T. Ishida, H. Kiwada, Accelerated blood clearance (ABC) phenomenon upon repeated injection of PEGylated liposomes. Int. J. Pharm. 354(1), 56–62 (2008)

    Article  Google Scholar 

  53. X. Xu, W. Ho, X. Zhang, N. Bertrand, O. Farokhzad, Cancer nanomedicine: from targeted delivery to combination therapy. Trends. Mol. Med. 21(4), 223–232 (2015)

    Article  Google Scholar 

  54. A. Akbarzadeh, R. Rezaei-Sadabady, S. Davaran, S.W. Joo, N. Zarghami, Y. Hanifehpour et al., Liposome: classification, preparation, and applications. Nanoscale Res. Lett. 8(1), 102 (2013)

    Article  ADS  Google Scholar 

  55. K.B. Knudsen, H. Northeved, P.K. Ek, A. Permin, T. Gjetting, T.L. Andresen et al., In vivo toxicity of cationic micelles and liposomes. Nanomedicine 11(2), 467–477 (2015)

    Article  Google Scholar 

  56. K.B. Johnsen, J.M. Gudbergsson, M.N. Skov, L. Pilgaard, T. Moos, M. Duroux, A comprehensive overview of exosomes as drug delivery vehicles—endogenous nanocarriers for targeted cancer therapy. Biochim. Biophys. Acta 1846(1), 75–87 (2014)

    Google Scholar 

  57. S.M. van Dommelen, P. Vader, S. Lakhal, S. Kooijmans, W.W. van Solinge, M.J. Wood et al., Microvesicles and exosomes: opportunities for cell-derived membrane vesicles in drug delivery. J. Control Release. 161(2), 635–644 (2012)

    Article  Google Scholar 

  58. S.C. Jang, O.Y. Kim, C.M. Yoon, D.-S. Choi, T.-Y. Roh, J. Park et al., Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano. 7(9), 7698–7710 (2013)

    Article  Google Scholar 

  59. Y. Tian, S. Li, J. Song, T. Ji, M. Zhu, G.J. Anderson et al., A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials 35(7), 2383–2390 (2014)

    Article  Google Scholar 

  60. X. Zhuang, X. Xiang, W. Grizzle, D. Sun, S. Zhang, R.C. Axtell et al., Treatment of brain inflammatory diseases by delivering exosome encapsulated anti-inflammatory drugs from the nasal region to the brain. Mol. Ther. 19(10), 1769–1779 (2011)

    Article  Google Scholar 

  61. H. Choi, Y.-S. Lee, D.W. Hwang, D.S. Lee, Translational radionanomedicine: a clinical perspective. Eur. J. Nanomed. 8(2), 71–84 (2016)

    Article  Google Scholar 

  62. A. Nikolopoulou, A. Amor-Coarasa, T. Wuestemann, I. Matei, A. Hoshino, S. DiMagno et al., Tumor exosomes as molecular probes to detect breast cancer pre-metastatic niches: radiolabeling with I-131 and tissue uptake studies in “naïve” nude mice. J. Nucl. Med. 57(supplement 2), 524 (2016)

    Google Scholar 

  63. S. Vallabhajosula, D. Lyden, H.P. Selgas, A. Nikolopoulou, Radiolabeled exosomes for the early detection of metastases and to predict breast cancer premetastatic niche: Annual rept. 1 Aug 2014–31 Jul 2015 Cornell University Medical Coll

    Google Scholar 

  64. D.S. Lee, C. Hongyoon, Y.S. Lee, J.M. Jeong, Y.S Gho, S.C. Jang SC, Method for labeling exosomes with radioactive substance and use thereof. Google Patents, 2015

    Google Scholar 

  65. Y. Takahashi, M. Nishikawa, H. Shinotsuka, Y. Matsui, S. Ohara, T. Imai et al., Visualization and in vivo tracking of the exosomes of murine melanoma B16-BL6 cells in mice after intravenous injection. J. Biotechnol. 165(2), 77–84 (2013)

    Article  Google Scholar 

  66. T. Imai, Y. Takahashi, M. Nishikawa, K. Kato, M. Morishita, T. Yamashita et al., Macrophage-dependent clearance of systemically administered B16BL6-derived exosomes from the blood circulation in mice. J. Extracell Vesicles 4(1), 26238 (2015)

    Article  Google Scholar 

  67. V. Hornung, F. Bauernfeind, A. Halle, E.O. Samstad, H. Kono, K.L. Rock et al., Silica crystals and aluminum salts activate the NALP3 inflammasome through phagosomal destabilization. Nat. Immunol. 9(8), 847–856 (2008)

    Article  Google Scholar 

  68. O.P. Wiklander, J.Z. Nordin, A. O’Loughlin, Y. Gustafsson, G. Corso, I. Mäger et al., Extracellular vesicle in vivo biodistribution is determined by cell source, route of administration and targeting. Extracell Vesicles 4(1), 26316 (2015)

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University College of Medicine, Seoul, 03080, Republic of Korea

    Seunggyun Ha & Dong Soo Lee

  2. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, 03080, Republic of Korea

    Seunggyun Ha & Dong Soo Lee

  3. Korea Brain Research Institute, Daegu, Republic of Korea

    Dong Soo Lee

Authors
  1. Seunggyun Ha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dong Soo Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Seunggyun Ha .

Editor information

Editors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University, Seoul, Korea (Republic of)

    Dong Soo Lee

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Ha, S., Lee, D.S. (2018). Endogenous Radionanomedicine: Validation of Therapeutic Potential. In: Lee, D. (eds) Radionanomedicine. Biological and Medical Physics, Biomedical Engineering. Springer, Cham. https://doi.org/10.1007/978-3-319-67720-0_9

Download citation

Publish with us

Policies and ethics

Search

Navigation