Skip to main content

Advertisement

SpringerLink
Log in

Perspective in Nuclear Theranostics Using Exosome for the Brain

  • Perspective
  • Published:
Nuclear Medicine and Molecular Imaging Aims and scope Submit manuscript

Abstract

Owing to its highly biocompatible property as naturally produced nanoscale particle and drug carrying ability, exosome has attracted much interest in the biomedical area. Versatile functions of exosome in biological system play an important role in elucidating mysterious and unknown biological processes and pathological disease progression. For usage of exosome as brain disease therapeutics, even though the ability of exosomes crossing blood brain barrier (BBB) is not well clearly proven, the small size and their own characteristics possessing cell-derived molecular contents may provide great and beneficial tools for brain delivery and brain-associated disease therapy. A variety of trials related to bioapplications using stem cell-derived exosome in regenerative therapy or autologous exosome shuttling inhibitor targeting brain disease-associated protein marker enhance possibility of exosome toward clinical application. The radionuclide PET or SPECT imaging of radiolabeled exosome will be clearly able to provide accurate clues for analyzing their whole body distribution, targeting efficacy, and the degree of non-specific tissue uptake. In this perspective, the practical information on thranostics of exosome for brain delivery and therapy is offered and radionuclide-based exosome applicability will be dealt with.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. He C, Zheng S, Luo Y, Wang B. Exosome Theranostics: biology and translational medicine. Theranostics. 2018;8:237–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Bunggulawa EJ, Wang W, Yin T, Wang N, Durkan C, Wang Y, et al. Recent advancements in the use of exosomes as drug delivery systems. J Nanobiotechnol. 2018;16:81–94.

    Article  CAS  Google Scholar 

  3. Pinheiro A, Silva AM, Teixeira JH, Gonçalves RM, Almeida MI, Barbosa MA, et al. Extracellular vesicles: intelligent delivery strategies for therapeutic applications. J Control Release. 2018;289:56–69.

    Article  CAS  PubMed  Google Scholar 

  4. Armstrong JPK, Stevens MM. Strategic design of extracellular vesicle drug delivery systems. Adv Drug Deliv Rev. 2018;130:12–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Lee K, Fraser K, Ghaddar B, Yang K, Kim E, Balaj L, et al. Multiplexed profiling of single extracellular vesicles. ACS Nano. 2018;12:494–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Contreras-Naranjo JC, Wu HJ, Ugaz VM. Microfluidics for exosome isolation and analysis: enabling liquid biopsy for personalized medicine. Lab Chip. 2017;17:3558–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Goodarzi P, Larijani B, Alavi-Moghadam S, Tayanloo-Beik A, Mohamadi-Jahani F, Ranjbaran N, et al. Mesenchymal stem cells-derived exosomes for wound regeneration. Adv Exp Med Biol. 2018;251:1–13.

    Google Scholar 

  8. Ebrahim N, Ahmed IA, Hussien NI, Dessouky AA, Farid AS, Elshazly AM, et al. Mesenchymal stem cell-derived exosomes ameliorated diabetic nephropathy by autophagy induction through the mTOR signaling pathway. Cell. 2018;7:E226.1–E226.10.

    Google Scholar 

  9. Gartz M, Darlington A, Afzal MZ, Strande JL. Exosomes exert cardioprotection in dystrophin-deficient cardiomyocytes via ERK1/2-p38/MAPK signaling. Sci Rep. 2018;8:16519–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Koyama Y, Ito T, Hasegawa A, Eriguchi M, Inaba T, Ushigusa T, et al. Exosomes derived from tumor cells genetically modified to express mycobacterium tuberculosis antigen: a novel vaccine for cancer therapy. Biotechnol Lett. 2016;38:1857–66.

    Article  CAS  PubMed  Google Scholar 

  11. van den Boorn JG, Dassler J, Coch C, Schlee M, Hartmann G. Exosomes as nucleic acid nanocarriers. Adv Drug Deliv Rev. 2013;65:331–5.

    Article  CAS  PubMed  Google Scholar 

  12. Vashisht M, Rani P, Onteru SK, Singh D. Curcumin encapsulated in milk exosomes resists human digestion and possesses enhanced intestinal permeability in vitro. Appl Biochem Biotechnol. 2017;183:993–1007.

    Article  CAS  PubMed  Google Scholar 

  13. Kim MS, Haney MJ, Zhao Y, Mahajan V, Deygen I, Klyachko NL, et al. Development of exosome-encapsulated paclitaxel to overcome MDR in cancer cells. Nanomedicine. 2016;12:655–64.

    Article  CAS  PubMed  Google Scholar 

  14. Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharmacol Sin. 2017;38:754–63.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kamerkar S, LeBleu VS, Sugimoto H, Yang S, Ruivo CF, Melo SA, et al. Exosomes facilitate therapeutic targeting of oncogenic KRAS in pancreatic cancer. Nature. 2017;546:498–503.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Xu H, Liao C, Zuo P, Liu Z, Ye BC. Magnetic-based microfluidic device for on-chip isolation and detection of tumor-derived exosomes. Anal Chem. 2018;90:13451–8.

    Article  CAS  PubMed  Google Scholar 

  17. Fang S, Tian H, Li X, Jin D, Li X, Kong J, et al. Clinical application of a microfluidic chip for immunocapture and quantification of circulating exosomes to assist breast cancer diagnosis and molecular classification. PLoS One. 2017;12:e0175050.1–e0175050.13.

    Google Scholar 

  18. Shao H, Chung J, Lee K, Balaj L, Min C, Carter BS, et al. Chip-based analysis of exosomal mRNA mediating drug resistance in glioblastoma. Nat Commun. 2015;6:6999–7018.

    Article  CAS  PubMed  Google Scholar 

  19. Fraser KB, Rawlins AB, Clark RG, Alcalay RN, Standaert DG, Liu N, et al. Ser(P)-1292 LRRK2 in urinary exosomes is elevated in idiopathic Parkinson’s disease. Mov Disord. 2016;31:1543–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Lai RC, Arslan F, Lee MM, Sze NS, Choo A, Chen TS, et al. Exosome secreted by MSC reduces myocardial ischemia/reperfusion injury. Stem Cell Res. 2010;4:214–22.

    Article  CAS  PubMed  Google Scholar 

  21. Arslan F, Lai RC, Smeets MB, Akeroyd L, Choo A, Aguor EN, 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. 2013;10:301–12.

    Article  CAS  PubMed  Google Scholar 

  22. Kim YJ, Yoo SM, Park HH, Lim HJ, Kim YL, Lee S, et al. Exosomes derived from human umbilical cord blood mesenchymal stem cells stimulates rejuvenation of human skin. Biochem Biophys Res Commun. 2017;493:1102–8.

    Article  CAS  PubMed  Google Scholar 

  23. Jarmalavičiūtė A, Tunaitis V, Pivoraitė U, Venalis A, Pivoriūnas A. Exosomes from dental pulp stem cells rescue human dopaminergic neurons from 6-hydroxy-dopamine-induced apoptosis. Cytotherapy. 2015;17:932–9.

    Article  CAS  PubMed  Google Scholar 

  24. Haney MJ, Klyachko NL, Zhao Y, Gupta R, Plotnikova EG, He Z. Exosomes as drug delivery vehicles for Parkinson’s disease therapy. J Control Release. 2015;207:18–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. El Bassit G, Patel RS, Carter G, Shibu V, Patel AA, Song S, et al. MALAT1 in human adipose stem cells modulates survival and alternative splicing of PKCδII in HT22 cells. Endocrinology. 2017;158:183–95.

    PubMed  Google Scholar 

  26. Chen KH, Chen CH, Wallace CG, Yuen CM, Kao GS, Chen YL, et al. Intravenous administration of xenogenic adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes markedly reduced brain infarct volume and preserved neurological function in rat after acute ischemic stroke. Oncotarget. 2016;7:74537–56.

    PubMed  PubMed Central  Google Scholar 

  27. Wang Y, Wang N, Cai B, Wang GY, Li J, Piao XX. In vitro model of the blood-brain barrier established by co-culture of primary cerebral microvascular endothelial and astrocyte cells. Neural Regen Res. 2015;10:2011–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. He Y, Yao Y, Tsirka SE, Cao Y. Cell-culture models of the blood-brain barrier. Stroke. 2014;45:2514–26.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Wang YI, Abaci HE, Shuler ML. Microfluidic blood-brain barrier model provides in vivo-like barrier properties for drug permeability screening. Biotechnol Bioeng. 2017;114:184–94.

    Article  CAS  PubMed  Google Scholar 

  30. Chen CC, Liu L, Ma F, Wong CW, Guo XE, Chacko JV, et al. Elucidation of exosome migration across the blood-brain barrier model in vitro. Cell Mol Bioeng. 2016;9:509–29.

    Article  CAS  PubMed  Google Scholar 

  31. Alvarez-Erviti L, Seow Y, Yin H, Betts C, Lakhal S, Wood MJ. Delivery of siRNA to the mouse brain by systemic injection of targeted exosomes. Nat Biotechnol. 2011;29:341–5.

    Article  CAS  PubMed  Google Scholar 

  32. Qu M, Lin Q, Huang L, Fu Y, Wang L, He S, et al. Dopamine-loaded blood exosomes targeted to brain for better treatment of Parkinson’s disease. J Control Release. 2018;287:156–66.

    Article  CAS  PubMed  Google Scholar 

  33. Zheng G, Huang R, Qiu G, Ge M, Wang J, Shu Q, et al. Mesenchymal stromal cell-derived extracellular vesicles: regenerative and immunomodulatory effects and potential applications in sepsis. Cell Tissue Res. 2018;374:1–15.

    Article  CAS  PubMed  Google Scholar 

  34. Cosenza S, Toupet K, Maumus M, Luz-Crawford P, Blanc-Brude O, Jorgensen C, et al. Mesenchymal stem cells-derived exosomes are more immunosuppressive than microparticles in inflammatory arthritis. Theranostics. 2018;8:1399–410.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Lapchak PA, Boitano PD, de Couto G, Marbán E. Intravenous xenogeneic human cardiosphere-derived cell extracellular vesicles (exosomes) improves behavioral function in small-clot embolized rabbits. Exp Neurol. 2018;307:109–17.

    Article  CAS  PubMed  Google Scholar 

  36. Cho BS, Kim JO, Ha DH, Yi YW. Exosomes derived from human adipose tissue-derived mesenchymal stem cells alleviate atopic dermatitis. Stem Cell Res Ther. 2018;9:187–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Li Y, Cheng Q, Hu G, Deng T, Wang Q, Zhou J, et al. Extracellular vesicles in mesenchymal stromal cells: a novel therapeutic strategy for stroke. Exp Ther Med. 2018;15:4067–79.

    PubMed  PubMed Central  Google Scholar 

  38. Ohno S, Takanashi M, Sudo K, Ueda S, Ishikawa A, Matsuyama N, et al. Systemically injected exosomes targeted to EGFR deliver antitumor microRNA to breast cancer cells. Mol Ther. 2013;21:185–91.

    Article  CAS  PubMed  Google Scholar 

  39. Lin KC, Yip HK, Shao PL, Wu SC, Chen KH, Chen YT, et al. Combination of adipose-derived mesenchymal stem cells (ADMSC) and ADMSC-derived exosomes for protecting kidney from acute ischemia-reperfusion injury. Int J Cardiol. 2016;216:173–85.

    Article  PubMed  Google Scholar 

  40. Busato A, Bonafede R, Bontempi P, Scambi I, Schiaffino L, Benati D, et al. Labeling and magnetic resonance imaging of exosomes isolated from adipose stem cells. Curr Protoc Cell Biol. 2017;75:3.44.1–3.44.15.

    Article  Google Scholar 

  41. Busato A, Bonafede R, Bontempi P, Scambi I, Schiaffino L, Benati D, et al. Magnetic resonance imaging of ultrasmall superparamagnetic iron oxide-labeled exosomes from stem cells: a new method to obtain labeled exosomes. Int J Nanomedicine. 2016;11:2481–90.

    CAS  PubMed  PubMed Central  Google Scholar 

  42. Morishita M, Takahashi Y, Nishikawa M, Sano K, Kato K, Yamashita T, 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. 2015;104:705–13.

    Article  CAS  PubMed  Google Scholar 

  43. Hwang DW, Choi H, Jang SC, Yoo MY, Park JY, Choi NE, et al. Noninvasive imaging of radiolabeled exosome-mimetic nanovesicle using (99m)Tc-HMPAO. Sci Rep. 2015;5:15636–46.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

This research was supported by a grant of the Research-Driven Hospital Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of Korea (HI14C1277) and National Research Foundation of Korea grant funded by Ministry of Science and ICT (MSIT) (2015M3C7A1028926, 2017M3C7A1048079).

Author information

Authors and Affiliations

  1. Department of Nuclear Medicine, Seoul National University Hospital, Seoul National University College of Medicine, 28 Yongon-Dong, Jongno-Gu, Seoul, 110-744, South Korea

    Do Won Hwang

  2. Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, and College of Medicine or College of Pharmacy, Seoul National University, Seoul, South Korea

    Do Won Hwang

Authors
  1. Do Won Hwang
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Do Won Hwang.

Ethics declarations

Conflict of Interest

Do Won Hwang declares no conflict of interest.

Ethical Approval

This perspective does not contain any studies with human participants or animals.

Informed Consent

As a review article, obtaining informed consent was waived.

Additional information

Publisher’s Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hwang, D.W. Perspective in Nuclear Theranostics Using Exosome for the Brain. Nucl Med Mol Imaging 53, 108–114 (2019). https://doi.org/10.1007/s13139-018-00567-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13139-018-00567-6

Keywords

Search

Navigation