Export file:

Format

  • RIS(for EndNote,Reference Manager,ProCite)
  • BibTex
  • Text

Content

  • Citation Only
  • Citation and Abstract

Drug delivery application of extracellular vesicles; insight into production, drug loading, targeting, and pharmacokinetics

Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, Tokyo, Japan

Extracellular vesicles (EVs) are secreted from any types of cells and shuttle between donor cells and recipient cells. Since EVs deliver their cargos such as proteins, nucleic acids, and other molecules for intercellular communication, they are considered as novel mode of drug delivery vesicles. EVs possess advantages such as inherent targeting ability and non-toxicity over conventional nanocarriers. Much efforts have so far been made for the application of EVs as a drug delivery carrier, however, basic techniques, such as mass-scale production, drug loading, and engineering of EVs are still limited. In this review, we summarize following four points. First, recent progress on the production method for EVs is described. Second, current techniques of drug loading methods are summarized. Third, targeting approach to specifically deliver cargo molecules for diseased sites by engineered EVs is discussed. Lastly, strategies to control pharmacokinetics and improve biodistribution are discussed.
  Figure/Table
  Supplementary
  Article Metrics

References

1. Allen T M and Cullis P R (2004) Drug delivery systems: entering the mainstream. Science 303: 1818-1822.    

2. Peer D, Karp J M, Hong S, et al. (2007) Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol 2: 751-760.    

3. Choi H S, Liu W, Misra P, et al. (2007) Renal clearance of quantum dots. Nat Biotechnol 25: 1165-1170.    

4. Matsumura Y and Maeda H (1986) A new concept for macromolecular therapeutics in cnacer chemotherapy: mechanism of tumoritropic accumulatio of proteins and the antitumor agents smancs. Cancer Res 46: 6387-6392.

5. Maeda H (2001) The enhanced permeability and retention (EPR) effect in tumor vasculature: the key role of tumor-selective macromolecular drug targeting. Adv Enzyme Regul 41: 189-207.    

6. Bae Y H and Park K (2011) Targeted drug delivery to tumors: myths, reality and possibility. J Control Release 153: 198-205.    

7. Wilhelm S, Tavares A J, Dai Q, et al. (2016) Analysis of nanoparticle delivery to tumours. Nat Rev Mater.1: 16014.

8. Raposo G and Stoorvogel W (2013) Extracellular vesicles: exosomes, microvesicles, and friends. J Cell Biol 200: 373-383.    

9. Lener T, Gimona M, Aigner L, et al. (2015) Applying extracellular vesicles based therapeutics in clinical trials-an ISEV position paper. J Extracell Vesicles 4: 41-31.

10. Heijnen H F, Schiel A E, Fijnheer R, et al. (1999) Activated platelets release two types of membrane vesicles: microvesicles by surface shedding and exosomes derived from exocytosis of multivesicular bodies and alpha-granules. Blood 94: 3791-3799.

11. Théry C, Zitvogel L, Amigorena S (2002) Exosomes: composition, biogenesis and function. Nat Rev Immunol 2: 569-579.

12. Valadi H, Ekström K, Bossios A, et al. (2007) Exosome-mediated transfer of mRNAs and microRNAs is a novel mechanism of genetic exchange between cells. Nat Cell Biol 9: 654-659.    

13. Gu H, Chen C, Hao X, et al. (2016) Sorting protein VPS33B regulates exosomal autocrine signaling to mediate hematopoiesis and leukemogenesis. J Clin Invest 126: 4537-4553.    

14. Zomer A, Maynard C, Verweij F J, et al. (2015) In vivo imaging reveals extracellular vesicle-mediated phenocopying of metastatic behavior. Cell 161: 1046-1057.    

15. Lai C P, Kim E Y, Badr C E, et al. (2015) Visualization and tracking of tumour extracellular vesicle delivery and RNA translation using multiplexed reporters. Nat Commun 6: 7029.    

16. Yamashita T, Takahashi Y, Nishikawa M, et al. (2016) Effect of exosome isolation methods on physicochemical properties of exosomes and clearance of exosomes from the blood circulation. Eur J Pharm Biopharm 98: 1-8.    

17. Welton J L, Webber J P, Botos L, et al. (2015) Ready-made chromatography columns for extracellular vesicle isolation from plasma. J Extracell Vesicles 4: 1-9.

18. Böing A N, Pol E, Grootemaat A E, et al. (2014) Single-step isolation of extracellular vesicles from plasma by size-exclusion chromatography. Int Meet Isev Rotterdam 3: 1-11.

19. Nakai W, Yoshida T, Diez D, et al. (2016) A novel affinity-based method for the isolation of highly purified extracellular vesicles. Sci Rep 6: 33935.    

20. Christianson H C, Svensson K J, Kuppevelt T H, et al. (2013) Cancer cell exosomes depend on cell-surface heparan sulfate proteoglycans for their internalization and functional activity. Proc Natl Acad Sci.110: 17380.

21 Balaj L, Atai N A, Chen W, et al. (2015) Heparin affinity purification of extracellular vesicles. Sci Rep 5: 10266.

22. Munagala R, Aqil F, Jeyabalan J, et al. (2016) Bovine milk-derived exosomes for drug delivery. Cancer Lett 371: 48-61.    

23 Watson D C, Bayik D, Srivatsan A, et al. (2016) Efficient production and enhanced tumor delivery of engineered extracellular vesicles. Biomaterials 105: 195-205.    

24 Wahlgren J, Karlson T, Brisslert M, et al. (2012) Plasma exosomes can deliver exogenous short interfering RNA to monocytes and lymphocytes. Nucleic Acids Res 40: e130.

25 Wang Q, Zhuang X, Mu J, et al. (2013) Delivery of therapeutic agents by nanoparticles made of grapefruit-derived lipids. Nat Commun 4: 1867.

26 Zhang M, Viennois E, Prasad M, et al. (2016) Edible ginger-derived nanoparticles: a novel therapeutic approach for the prevention and treatment of inflammatory bowel disease and colitis-associated cancer. Biomaterials 101: 321-340.    

27 Wurm F M (2004) Production of recombinant protein therapeutics in cultivated mammalian cells. Nat Biotechnol 22: 1393-1398.    

28 Pisitkun T, Shen R F, Knepper M A (2004) Identification and proteomic profiling of exosomes in human urine. Proc Natl Acad Sci 101: 13368-13373.    

29 Record M (2013) Exosome-like nanoparticles from food: protective nanoshuttles for bioactive cargo. Mol Ther 21: 1294-1296.    

30 Izumi H, Tsuda M, Sato Y, et al. (2015) Bovine milk exosomes contain microRNA and mRNA and are taken up by human macrophages. J Dairy Sci 98: 2920-2933.    

31 Pieters B, Arntz O J, Bennink M B, et al. (2015) Commercial cow milk contains physically stable extracellular vesicles expressing immunoregulatory TGF-β. Plos One 10: e0121123.

32 Kosaka N, Izumi H, Sekine K, et al. (2010) MicroRNA as a new immune-regulatory agent in breast milk. Silence 1: 7.

33 Hata T, Muraka