Display options
Cite
Heidarzadeh M, Gürsoy-Özdemir Y, Kaya M, et al. Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls. Cell Biosci. 2021;11(1):142doi: 10.1186/s13578-021-00650-0.
Heidarzadeh, M., Gürsoy-Özdemir, Y., Kaya, M., Eslami Abriz, A., Zarebkohan, A., Rahbarghazi, R., & Sokullu, E. (2021). Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls. Cell & bioscience, 11(1), 142. https://doi.org/10.1186/s13578-021-00650-0
Heidarzadeh, Morteza, et al. "Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls." Cell & bioscience vol. 11,1 (2021): 142. doi: https://doi.org/10.1186/s13578-021-00650-0
Heidarzadeh M, Gürsoy-Özdemir Y, Kaya M, Eslami Abriz A, Zarebkohan A, Rahbarghazi R, Sokullu E. Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls. Cell Biosci. 2021 Jul 22;11(1):142. doi: 10.1186/s13578-021-00650-0. PMID: 34294165; PMCID: PMC8296716.
Copy Download .nbib Format: NLM
Share it on

Cell Biosci. 2021 Jul 22;11(1):142. doi: 10.1186/s13578-021-00650-0.

Exosomal delivery of therapeutic modulators through the blood-brain barrier; promise and pitfalls.

Cell & bioscience

Morteza Heidarzadeh, Yasemin Gürsoy-Özdemir, Mehmet Kaya, Aysan Eslami Abriz, Amir Zarebkohan, Reza Rahbarghazi, Emel Sokullu

Affiliations

  1. Koç University Research Center for Translational Medicine (KUTTAM), Rumeli Feneri, 34450, Sariyer, Istanbul, Turkey.
  2. Neurology Department, Koç University School of Medicine, Rumeli Feneri, 34450, Sariyer, Istanbul, Turkey.
  3. Physiology Department, Koç University School of Medicine, Rumeli Feneri, 34450, Sariyer, Istanbul, Turkey.
  4. Department of Medical Nanotechnology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran.
  5. Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected].
  6. Department of Applied Cell Sciences, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran. [email protected].
  7. Koç University Research Center for Translational Medicine (KUTTAM), Rumeli Feneri, 34450, Sariyer, Istanbul, Turkey. [email protected].
  8. Biophysics Department, Koç University School of Medicine, Rumeli Feneri, 34450, Sariyer, Istanbul, Turkey. [email protected].

PMID: 34294165 PMCID: PMC8296716 DOI: 10.1186/s13578-021-00650-0

Abstract

Nowadays, a large population around the world, especially the elderly, suffers from neurological inflammatory and degenerative disorders/diseases. Current drug delivery strategies are facing different challenges because of the presence of the BBB, which limits the transport of various substances and cells to brain parenchyma. Additionally, the low rate of successful cell transplantation to the brain injury sites leads to efforts to find alternative therapies. Stem cell byproducts such as exosomes are touted as natural nano-drug carriers with 50-100 nm in diameter. These nano-sized particles could harbor and transfer a plethora of therapeutic agents and biological cargos to the brain. These nanoparticles would offer a solution to maintain paracrine cell-to-cell communications under healthy and inflammatory conditions. The main question is that the existence of the intact BBB could limit exosomal trafficking. Does BBB possess some molecular mechanisms that facilitate the exosomal delivery compared to the circulating cell? Although preliminary studies have shown that exosomes could cross the BBB, the exact molecular mechanism(s) beyond this phenomenon remains unclear. In this review, we tried to compile some facts about exosome delivery through the BBB and propose some mechanisms that regulate exosomal cross in pathological and physiological conditions.

© 2021. The Author(s).

Keywords: Blood–brain barrier; Delivery; Exosomes

References

  1. Int J Pharm. 2015 Nov 10;495(1):439-446 - PubMed
  2. Int J Biochem Cell Biol. 2012 Sep;44(9):1574-84 - PubMed
  3. Cell Biosci. 2019 Feb 15;9:19 - PubMed
  4. Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8033-7 - PubMed
  5. Nat Med. 2000 Jul;6(7):769-75 - PubMed
  6. Lung. 2017 Aug;195(4):445-453 - PubMed
  7. J Cell Physiol. 2004 Mar;198(3):359-69 - PubMed
  8. Mol Aspects Med. 2018 Apr;60:62-68 - PubMed
  9. Exp Neurol. 2018 Sep;307:99-108 - PubMed
  10. J Biol Chem. 2018 Sep 28;293(39):15277-15289 - PubMed
  11. Nat Immunol. 2008 Aug;9(8):847-56 - PubMed
  12. Pharmacol Ther. 2017 Jun;174:63-78 - PubMed
  13. Mol Pharm. 2015 Oct 5;12(10):3650-7 - PubMed
  14. Proc Natl Acad Sci U S A. 1997 Jul 8;94(14):7326-30 - PubMed
  15. Neuroscience. 2007 Dec 5;150(2):498-509 - PubMed
  16. Adv Sci (Weinh). 2018 Jan 30;5(4):1700611 - PubMed
  17. Nat Rev Immunol. 2002 Aug;2(8):569-79 - PubMed
  18. AAPS J. 2017 Jul;19(4):910-920 - PubMed
  19. J Control Release. 2018 Oct 10;287:156-166 - PubMed
  20. Bioconjug Chem. 2014 Oct 15;25(10):1777-84 - PubMed
  21. Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10592-7 - PubMed
  22. Curr Biol. 2018 Apr 23;28(8):R435-R444 - PubMed
  23. Biomaterials. 2018 Sep;178:302-316 - PubMed
  24. Cell Mol Life Sci. 2019 May;76(10):1987-2002 - PubMed
  25. Cancer Res. 2015 Jun 15;75(12):2520-9 - PubMed
  26. Mol Cancer. 2020 Mar 25;19(1):66 - PubMed
  27. Genome Biol. 2009;10(8):235 - PubMed
  28. Biomaterials. 2017 Oct;142:1-12 - PubMed
  29. ACS Nano. 2016 Mar 22;10(3):3323-33 - PubMed
  30. J Cereb Blood Flow Metab. 1999 Sep;19(9):1038-50 - PubMed
  31. Nat Cell Biol. 2018 Mar;20(3):228-230 - PubMed
  32. Acta Biomater. 2017 Jul 15;57:274-284 - PubMed
  33. ACS Nano. 2019 Dec 24;13(12):13853-13865 - PubMed
  34. Adv Drug Deliv Rev. 2013 Mar;65(3):331-5 - PubMed
  35. J Control Release. 2015 Jun 10;207:18-30 - PubMed
  36. FEBS Lett. 2019 Sep;593(17):2306-2318 - PubMed
  37. Adv Mater. 2017 Apr;29(13): - PubMed
  38. Pharmaceutics. 2021 Feb 28;13(3): - PubMed
  39. Mol Pharm. 2017 Jul 3;14(7):2177-2196 - PubMed
  40. Brain Res. 2015 Aug 18;1617:63-71 - PubMed
  41. Neurosurgery. 1994 Aug;35(2):294-8; discussion 298 - PubMed
  42. Sci Adv. 2020 Dec 11;6(50): - PubMed
  43. J Biol Chem. 2012 Feb 3;287(6):3842-9 - PubMed
  44. J Hematol Oncol. 2018 Jul 31;11(1):97 - PubMed
  45. J Extracell Vesicles. 2015 Apr 20;4:26316 - PubMed
  46. Curr Stem Cell Res Ther. 2019;14(7):570-578 - PubMed
  47. Biochem Biophys Res Commun. 2016 Mar 25;472(1):53-9 - PubMed
  48. Biochim Biophys Acta. 2009 Dec;1793(12):1901-16 - PubMed
  49. Nanomedicine. 2011 Jun;7(3):315-23 - PubMed
  50. Sci Rep. 2016 Feb 25;6:21933 - PubMed
  51. Adv Drug Deliv Rev. 2008 Dec 14;60(15):1638-49 - PubMed
  52. Curr Pharm Des. 2004;10(13):1439-55 - PubMed
  53. Acta Neuropathol. 2011 Jul;122(1):1-9 - PubMed
  54. J Cell Physiol. 2019 Jun;234(6):8249-8258 - PubMed
  55. Endocrinology. 2004 Aug;145(8):3935-40 - PubMed
  56. Nat Neurosci. 2015 Nov;18(11):1584-93 - PubMed
  57. J Control Release. 2016 Feb 28;224:77-85 - PubMed
  58. Nat Commun. 2018 Jun 15;9(1):2359 - PubMed
  59. J Cereb Blood Flow Metab. 2018 Apr;38(4):727-740 - PubMed
  60. Front Neurosci. 2018 Feb 06;12:37 - PubMed
  61. Sci Rep. 2015 Dec 03;5:17543 - PubMed
  62. J Nanobiotechnology. 2018 Aug 30;16(1):61 - PubMed
  63. Science. 1995 Nov 10;270(5238):988-91 - PubMed
  64. Adv Drug Deliv Rev. 2007 Mar 30;59(2-3):141-52 - PubMed
  65. Clin Genet. 2011 Oct;80(4):305-18 - PubMed
  66. Traffic. 2009 Apr;10(4):364-71 - PubMed
  67. Semin Cell Dev Biol. 2017 Jul;67:48-55 - PubMed
  68. Bioact Mater. 2020 Oct 09;6(4):963-974 - PubMed
  69. Nat Biotechnol. 2011 Apr;29(4):341-5 - PubMed
  70. Mol Neurobiol. 2019 Jun;56(6):4566-4581 - PubMed
  71. J Histochem Cytochem. 2002 Jan;50(1):43-55 - PubMed
  72. Biochim Biophys Acta. 2009 Apr;1788(4):842-57 - PubMed
  73. Adv Ther (Weinh). 2019 Nov;2(11): - PubMed
  74. Theranostics. 2020 Jun 12;10(16):7422-7435 - PubMed
  75. Nature. 2016 Dec 8;540(7632):284-287 - PubMed
  76. J Immunol. 2017 Nov 15;199(10):3559-3570 - PubMed
  77. Nat Cell Biol. 2018 Mar;20(3):332-343 - PubMed
  78. Biochemistry. 2009 Jul 21;48(28):6571-84 - PubMed
  79. FASEB J. 2018 Jan;32(1):168-182 - PubMed
  80. Biochem Biophys Res Commun. 2017 Jan 29;483(1):602-608 - PubMed
  81. J Cell Sci. 2012 Sep 1;125(Pt 17):4049-57 - PubMed
  82. Glia. 2018 Jan;66(1):126-144 - PubMed
  83. Glycobiology. 2009 May;19(5):479-87 - PubMed
  84. Mol Ther. 2002 Feb;5(2):104-14 - PubMed
  85. Pharmacol Rev. 2002 Dec;54(4):561-87 - PubMed
  86. Curr Drug Targets. 2017;18(12):1386-1391 - PubMed
  87. Langmuir. 2013 Nov 26;29(47):14639-47 - PubMed
  88. Anal Chem. 2020 Apr 21;92(8):6010-6018 - PubMed
  89. J Biol Chem. 2009 Jul 31;284(31):21036-46 - PubMed
  90. ACS Appl Mater Interfaces. 2016 Mar 23;8(11):6790-5 - PubMed
  91. CNS Drugs. 2017 Feb;31(2):109-133 - PubMed
  92. Adv Drug Deliv Rev. 2007 Jul 10;59(6):478-90 - PubMed
  93. Sci Rep. 2017 Aug 25;7(1):9563 - PubMed
  94. J Am Chem Soc. 2005 Dec 7;127(48):16892-9 - PubMed
  95. Vaccine. 2012 Nov 26;30(50):7229-37 - PubMed
  96. J Cell Physiol. 2013 Jul;228(7):1487-95 - PubMed
  97. Nat Biomed Eng. 2020 Jan;4(1):69-83 - PubMed
  98. Trends Neurosci. 1990 May;13(5):174-8 - PubMed
  99. Neuropharmacology. 2017 Jul 1;120:4-7 - PubMed
  100. Biomaterials. 2018 Oct;180:117-129 - PubMed
  101. Biochem Biophys Res Commun. 2010 Aug 27;399(3):384-90 - PubMed
  102. Mol Ther. 2013 Jul;21(7):1345-57 - PubMed
  103. Annu Rev Pharmacol Toxicol. 2021 Jan 6;61:291-308 - PubMed
  104. J Autoimmun. 2018 Jul;91:34-44 - PubMed
  105. DNA Cell Biol. 2015 Jul;34(7):459-63 - PubMed
  106. Nature. 2018 Jun;558(7709):307-312 - PubMed
  107. ACS Appl Mater Interfaces. 2017 Aug 23;9(33):27441-27452 - PubMed
  108. J Biol Chem. 2018 Nov 9;293(45):17317-17335 - PubMed
  109. Lancet Neurol. 2008 Jan;7(1):84-96 - PubMed
  110. Nat Cell Biol. 2008 Aug;10(8):923-34 - PubMed
  111. J Cell Sci. 2013 Dec 15;126(Pt 24):5553-65 - PubMed
  112. Nanomedicine. 2018 Jan;14(1):195-204 - PubMed
  113. Mol Cell Neurosci. 2006 Apr;31(4):642-8 - PubMed
  114. Cell Mol Life Sci. 2019 Mar;76(6):1081-1092 - PubMed
  115. J Nanobiotechnology. 2018 Oct 16;16(1):81 - PubMed
  116. Gene. 2016 Jan 10;575(2 Pt 2):377-384 - PubMed
  117. Mediators Inflamm. 2016;2016:1927348 - PubMed
  118. J Control Release. 2020 Jan 10;317:273-281 - PubMed
  119. J Cell Physiol. 2009 Mar;218(3):612-22 - PubMed
  120. J Control Release. 2019 Apr 10;299:149-164 - PubMed
  121. Int J Parasitol. 2020 Aug;50(9):655-661 - PubMed
  122. Proteomics Clin Appl. 2007 Nov;1(11):1446-61 - PubMed
  123. Adv Drug Deliv Rev. 2013 Mar;65(3):336-41 - PubMed
  124. ACS Nano. 2013 Sep 24;7(9):7698-710 - PubMed
  125. Sci Rep. 2015 May 26;5:10112 - PubMed
  126. Lab Invest. 2009 Nov;89(11):1317-28 - PubMed
  127. Mol Ther. 2014 Jul;22(7):1333-1341 - PubMed
  128. Mol Membr Biol. 2014 Aug;31(5):152-67 - PubMed
  129. Mol Biol Cell. 2003 Jul;14(7):2689-705 - PubMed
  130. Biomolecules. 2018 Nov 14;8(4): - PubMed
  131. Expert Opin Drug Deliv. 2019 Mar;16(3):271-285 - PubMed
  132. Angew Chem Int Ed Engl. 2007;46(23):4342-5 - PubMed
  133. Biochim Biophys Acta Biomembr. 2019 Sep 1;1861(9):1579-1591 - PubMed
  134. J Control Release. 2020 Oct 10;326:599-614 - PubMed
  135. Biochem Biophys Res Commun. 2018 Jul 20;502(3):324-331 - PubMed
  136. Nat Nanotechnol. 2011 Oct 16;6(11):747-54 - PubMed
  137. J Neurosci Res. 2018 Jan;96(1):45-52 - PubMed
  138. Proc Natl Acad Sci U S A. 2016 Feb 23;113(8):E968-77 - PubMed
  139. Eur J Pharm Biopharm. 2020 Sep;154:259-269 - PubMed
  140. Ann Biomed Eng. 2010 Apr;38(4):1463-72 - PubMed
  141. Biomaterials. 2017 Dec;147:155-168 - PubMed
  142. J Nanobiotechnology. 2019 Feb 19;17(1):29 - PubMed
  143. Curr Pharm Des. 2020;26(13):1405-1416 - PubMed
  144. Langmuir. 2005 Nov 8;21(23):10348-54 - PubMed
  145. Immun Ageing. 2019 May 13;16:10 - PubMed
  146. Biotechnol Bioeng. 2017 Jan;114(1):184-194 - PubMed
  147. Adv Drug Deliv Rev. 2016 Feb 1;97:111-43 - PubMed
  148. Mol Pharm. 2019 Jan 7;16(1):292-304 - PubMed
  149. Int J Cancer. 2016 Jan 1;138(1):14-21 - PubMed
  150. Cell Mol Neurobiol. 2021 Apr;41(3):551-562 - PubMed
  151. Cell Tissue Res. 2014 Mar;355(3):701-15 - PubMed
  152. Front Pharmacol. 2019 Nov 21;10:1346 - PubMed
  153. Circ Res. 2005 Sep 16;97(6):512-23 - PubMed
  154. Acta Pharmacol Sin. 2017 Jun;38(6):754-763 - PubMed
  155. J Neurochem. 2018 Sep;146(6):735-752 - PubMed
  156. J Parkinsons Dis. 2017;7(4):569-576 - PubMed
  157. Iran J Pharm Res. 2018 Summer;17(3):1068-1080 - PubMed
  158. Biomaterials. 2014 Feb;35(7):2383-90 - PubMed
  159. Int J Pharm. 2017 Aug 7;528(1-2):675-691 - PubMed
  160. Theranostics. 2018 Feb 2;8(5):1195-1212 - PubMed
  161. Nat Commun. 2016 Jul 25;7:12276 - PubMed
  162. J Drug Target. 2000;8(6):413-24 - PubMed
  163. J Neuroinflammation. 2012 Jul 06;9:161 - PubMed
  164. Biomaterials. 2019 Jan;190-191:24-37 - PubMed
  165. Nat Rev Mol Cell Biol. 2009 Aug;10(8):513-25 - PubMed
  166. Genomics Proteomics Bioinformatics. 2015 Feb;13(1):17-24 - PubMed
  167. Curr Opin Struct Biol. 2017 Aug;45:109-115 - PubMed
  168. EMBO J. 2011 Aug 31;30(17):3481-500 - PubMed
  169. Curr Pharm Des. 2013;19(41):7203-18 - PubMed
  170. Fluids Barriers CNS. 2012 Nov 09;9(1):23 - PubMed
  171. Curr Pharm Des. 2017;23(40):6206-6214 - PubMed
  172. J Mol Biol. 2004 Sep 3;342(1):171-82 - PubMed
  173. Cell Rep. 2013 Dec 12;5(5):1159-68 - PubMed
  174. Mol Ther. 2012 May;20(5):960-71 - PubMed
  175. Signal Transduct Target Ther. 2019 Aug 30;4:33 - PubMed
  176. J Biol Chem. 1996 Sep 27;271(39):24048-54 - PubMed
  177. Cell Mol Bioeng. 2016 Dec;9(4):509-529 - PubMed
  178. Traffic. 2010 May;11(5):675-87 - PubMed
  179. Histol Histopathol. 2018 Jan;33(1):1-10 - PubMed
  180. Semin Cancer Biol. 2014 Oct;28:3-13 - PubMed
  181. Noncoding RNA. 2018 Dec 25;5(1): - PubMed
  182. Nat Med. 2013 Dec;19(12):1584-96 - PubMed
  183. Arch Immunol Ther Exp (Warsz). 2006 Mar-Apr;54(2):75-84 - PubMed
  184. Int Immunopharmacol. 2019 Feb;67:268-280 - PubMed
  185. Nano Lett. 2019 Jun 12;19(6):3422-3431 - PubMed
  186. Res Pharm Sci. 2018 Aug;13(4):288-303 - PubMed
  187. Am J Physiol Cell Physiol. 2004 Jun;286(6):C1213-28 - PubMed
  188. J Microbiol Biotechnol. 2015 Jan;25(1):119-26 - PubMed
  189. Adv Pharmacol. 2014;71:147-63 - PubMed
  190. CNS Neurosci Ther. 2012 Aug;18(8):609-15 - PubMed
  191. Exp Neurol. 2012 Jan;233(1):283-91 - PubMed
  192. Cancer Lett. 2016 Feb 1;371(1):48-61 - PubMed
  193. Sci Rep. 2019 Jun 4;9(1):8278 - PubMed
  194. Diabetes Obes Metab. 2017 Sep;19 Suppl 1:137-146 - PubMed
  195. Cancer Res. 2010 Feb 15;70(4):1668-78 - PubMed
  196. Theranostics. 2020 Feb 10;10(8):3474-3487 - PubMed
  197. Mol Pharm. 2013 May 6;10(5):1473-91 - PubMed
  198. J Neurovirol. 2016 Apr;22(2):129-39 - PubMed
  199. Nat Cell Biol. 2012 Oct;14(10):1036-45 - PubMed
  200. Nat Nanotechnol. 2017 Oct;12(10):974-979 - PubMed
  201. Mol Med Rep. 2012 Apr;5(4):935-42 - PubMed
  202. Cell Mol Immunol. 2010 Jan;7(1):11-9 - PubMed
  203. Pharm Res. 2008 Oct;25(10):2216-30 - PubMed
  204. Mol Cancer Res. 2017 Jun;15(6):723-734 - PubMed
  205. iScience. 2019 Jan 25;11:205-223 - PubMed
  206. J Biol Chem. 2011 Nov 18;286(46):40069-74 - PubMed
  207. Mol Ther. 2013 Jan;21(1):185-91 - PubMed
  208. Arterioscler Thromb Vasc Biol. 2016 Feb;36(2):339-49 - PubMed
  209. Biomaterials. 2018 Jan;150:137-149 - PubMed
  210. ACS Appl Mater Interfaces. 2018 Apr 18;10(15):12341-12350 - PubMed
  211. Brain Behav Immun. 2018 Mar;69:556-567 - PubMed
  212. Cell Mol Life Sci. 2007 Feb;64(3):356-64 - PubMed
  213. Proc Natl Acad Sci U S A. 2006 Jul 25;103(30):11172-7 - PubMed
  214. Ann N Y Acad Sci. 2017 Oct;1405(1):131-146 - PubMed
  215. J Extracell Vesicles. 2016 Jul 13;5:31295 - PubMed
  216. ACS Nano. 2017 Jan 24;11(1):69-83 - PubMed

Publication Types