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Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques

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Abstract

Background

Exosomes are natural nanoparticles that are involved in intercellular communication via transferring molecular information between cells. Recently, exosomes have been considered for exploitation as novel drug delivery systems due to their specific properties for carrying specific molecules and surface proteins.

Methods

In this study, U-87 cell derived exosomes have been investigated for delivery of a potent chemotherapeutic agent, paclitaxel (PTX). Two methods of loading were utilized to incorporate PTX in exosomes and the exosomes pharmaceutical and cytotoxic characterizations were determined.

Results

The drug loaded and empty exosomes were found to have particle size of 50–100 nm and zeta potential of ≈ − 20 mV. Loading capacity of 7.4 ng and 9.2 ng PTX into 1 μg of exosome total protein were also measured for incubation and sonication methods, respectively. Incorporation of PTX into exosomes significantly increased its cytotoxicity against U-87 cell line (59.92% cell viability) while it was found that the empty exosomes exhibited cell viability of 91.98%.

Conclusions

Loading method could affect the loading capacity of exosomes and their encapsulated chemotherapeutic molecule showed higher cytotoxicity into exosomes. These results promise exosomes as appropriate drug delivery system for glioblastoma multiform (GBM) treatment.

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References

  1. Tian Y, Li S, Song J, Ji T, Zhu M, Anderson GJ, et al. A doxorubicin delivery platform using engineered natural membrane vesicle exosomes for targeted tumor therapy. Biomaterials. 2014;35(7):2383–90.

    Article  CAS  Google Scholar 

  2. Luan X, Sansanaphongpricha K, Myers I, Chen H, Yuan H, Sun D. Engineering exosomes as refined biological nanoplatforms for drug delivery. Acta Pharm Sin B. 2017;38(6):754–63.

    Article  CAS  Google Scholar 

  3. Johnsen KB, Gudbergsson JM, Skov MN, Pilgaard L, Moos T, Duroux M. A comprehensive overview of exosomes as drug delivery vehicles—endogenous nanocarriers for targeted cancer therapy. BBA-Rev Cancer. 2014;1846(1):75–87.

    CAS  Google Scholar 

  4. Batrakova EV, Kim MS. Using exosomes, naturally-equipped nanocarriers, for drug delivery. J Control Release. 2015;219:396–405.

    Article  CAS  Google Scholar 

  5. Saari H, Lazaro-Ibanez E, Viitala T, Vuorimaa-Laukkanen E, Siljander P, Yliperttula M. Microvesicle-and exosome-mediated drug delivery enhances the cytotoxicity of paclitaxel in autologous prostate cancer cells. J Control Release. 2015;220:727–37.

    Article  CAS  Google Scholar 

  6. Jiang X-C, Gao J-Q. Exosomes as novel bio-carriers for gene and drug delivery. Int J Pharm. 2017;521(1–2):167–75.

    Article  CAS  Google Scholar 

  7. Jang SC, Kim OY, Yoon CM, Choi D-S, Roh T-Y, Park J, et al. Bioinspired exosome-mimetic nanovesicles for targeted delivery of chemotherapeutics to malignant tumors. ACS Nano. 2013;7(9):7698–710.

    Article  CAS  Google Scholar 

  8. Sun D, Zhuang X, Xiang X, Liu Y, Zhang S, Liu C, et al. A novel nanoparticle drug delivery system: the anti-inflammatory activity of curcumin is enhanced when encapsulated in exosomes. Mol Ther. 2010;18(9):1606–14.

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  10. Yang T, Martin P, Fogarty B, Brown A, Schurman K, Phipps R, et al. Exosome delivered anticancer drugs across the blood-brain barrier for brain cancer therapy in Danio rerio. Pharm Res. 2015;32(6):2003–14.

    Article  CAS  Google Scholar 

  11. Katakowski M, Chopp M. Exosomes as tools to suppress primary brain tumor. Cell Mol Neurobiol. 2016;36(3):343–52.

    Article  CAS  Google Scholar 

  12. Ganipineni LP, Danhier F, Préat V. Drug delivery challenges and future of chemotherapeutic nanomedicine for glioblastoma treatment. J Control Release. 2018;281:42–57.

    Article  CAS  Google Scholar 

  13. Gourlay J, Morokoff A, Luwor R, Zhu H-J, Kaye A, Stylli S. The emergent role of exosomes in glioma. J Clin Neurosci. 2017;35:13–23.

    Article  CAS  Google Scholar 

  14. Xin H, Sha X, Jiang X, Zhang W, Chen L, Fang X. Anti-glioblastoma efficacy and safety of paclitaxel-loading Angiopep-conjugated dual targeting PEG-PCL nanoparticles. Biomaterials. 2012;33(32):8167–76.

    Article  CAS  Google Scholar 

  15. Mu Q, Jeon M, Hsiao MH, Patton VK, Wang K, Press OW, et al. Stable and efficient paclitaxel nanoparticles for targeted glioblastoma therapy. Adv Healthc Mater. 2015;4(8):1236–45.

    Article  CAS  Google Scholar 

  16. Ganipineni LP, Ucakar B, Joudiou N, Bianco J, Danhier P, Zhao M, et al. Magnetic targeting of paclitaxel-loaded poly (lactic-co-glycolic acid)-based nanoparticles for the treatment of glioblastoma. Int J Nanomedicine. 2018;13:4509–21.

    Article  CAS  Google Scholar 

  17. Ruan C, Liu L, Lu Y, Zhang Y, He X, Chen X, et al. Substance P-modified human serum albumin nanoparticles loaded with paclitaxel for targeted therapy of glioma. Acta Pharm Sin B. 2018;8(1):85–96.

    Article  Google Scholar 

  18. Esfandyari-Manesh M, Mostafavi SH, Majidi RF, Koopaei MN, Ravari NS, Amini M, et al. Improved anticancer delivery of paclitaxel by albumin surface modification of PLGA nanoparticles. Daru. 2015;23(1):28.

    Article  Google Scholar 

  19. Chirio D, Gallarate M, Peira E, Battaglia L, Muntoni E, Riganti C, et al. Positive-charged solid lipid nanoparticles as paclitaxel drug delivery system in glioblastoma treatment. Eur J Pharm Biopharm. 2014;88(3):746–58.

    Article  CAS  Google Scholar 

  20. 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. Nanomed-Nanotechnol. 2016;12(3):655–64.

    Article  CAS  Google Scholar 

  21. Kamińska A, Platt M, Kasprzyk J, Kuśnierz-Cabala B, Gala-Błądzińska A, Woźnicka O, et al. Urinary extracellular vesicles: potential biomarkers of renal function in diabetic patients. J Diabetes Res. 2016;2016:1–12.

    Article  Google Scholar 

  22. Munagala R, Aqil F, Jeyabalan J, Gupta RC. Bovine milk-derived exosomes for drug delivery. Cancer Lett. 2016;371(1):48–61.

    Article  CAS  Google Scholar 

  23. Lane RE, Korbie D, Anderson W, Vaidyanathan R, Trau M. Analysis of exosome purification methods using a model liposome system and tunable-resistive pulse sensing. Sci Rep. 2015;5:7639.

    Article  Google Scholar 

  24. Welton JL, Webber JP, Botos L-A, Jones M, Clayton A. Ready-made chromatography columns for extracellular vesicle isolation from plasma. J Extracell Vesicles. 2015;4(1):27269.

    Article  Google Scholar 

  25. Helwa I, Cai J, Drewry MD, Zimmerman A, Dinkins MB, Khaled ML, et al. A comparative study of serum exosome isolation using differential ultracentrifugation and three commercial reagents. PLoS One. 2017;12(1):e0170628.

    Article  Google Scholar 

  26. Sokolova V, Ludwig A-K, Hornung S, Rotan O, Horn PA, Epple M, et al. Characterisation of exosomes derived from human cells by nanoparticle tracking analysis and scanning electron microscopy. Colloid Surface B. 2011;87(1):146–50.

    Article  CAS  Google Scholar 

  27. Marimpietri D, Petretto A, Raffaghello L, Pezzolo A, Gagliani C, Tacchetti C, et al. Proteome profiling of neuroblastoma-derived exosomes reveal the expression of proteins potentially involved in tumor progression. PLoS One. 2013;8(9):e75054.

    Article  CAS  Google Scholar 

  28. Haraszti RA, Didiot M-C, Sapp E, Leszyk J, Shaffer SA, Rockwell HE, et al. High-resolution proteomic and lipidomic analysis of exosomes and microvesicles from different cell sources. J Extracell Vesicles. 2016;5(1):32570.

    Article  Google Scholar 

  29. De Vrij J, Maas SL, Van Nispen M, Sena-Esteves M, Limpens RW, Koster AJ, et al. Quantification of nanosized extracellular membrane vesicles with scanning ion occlusion sensing. Nanomedicine-UK. 2013;8(9):1443–58.

    Article  Google Scholar 

  30. Pardakhty A, Varshosaz J, Rouholamini A. In vitro study of polyoxyethylene alkyl ether niosomes for delivery of insulin. Int J Pharm. 2007;328(2):130–41.

    Article  CAS  Google Scholar 

  31. Agrawal AK, Aqil F, Jeyabalan J, Spencer WA, Beck J, Gachuki BW, et al. Milk-derived exosomes for oral delivery of paclitaxel. Nanomed-Nanotechnol. 2017;13(5):1627–36.

    Article  CAS  Google Scholar 

  32. Beit-Yannai E, Tabak S, Stamer WD. Physical exosome: exosome interactions. J Cell Mol Med. 2018;22(3):2001–6.

    Article  Google Scholar 

  33. Kato K, Kobayashi M, Hanamura N, Akagi T, Kosaka N, Ochiya T, et al. Electrokinetic evaluation of individual exosomes by on-chip microcapillary electrophoresis with laser dark-field microscopy. Jpn of Appl Phys. 2013;52(6S):06GK10.

    Article  Google Scholar 

  34. Hood JL, Scott MJ, Wickline SA. Maximizing exosome colloidal stability following electroporation. Anal Biochem. 2014;448:41–9.

    Article  CAS  Google Scholar 

  35. Parolini I, Federici C, Raggi C, Lugini L, Palleschi S, De Milito A et al. Microenvironmental pH is a key factor for exosome traffic in tumor cells. J Biol Chem 2009:jbc. M109. 041152.

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Acknowledgments

This work was supported by the Kerman University of Medical Sciences [grant No. 95000430], Kerman, Iran.

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Authors and Affiliations

  1. Pharmaceutics Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Soodeh Salarpour, Hamid Forootanfar & Abbas Pardakhty

  2. Department of Pharmaceutics, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Soodeh Salarpour & Abbas Pardakhty

  3. Department of Pharmaceutical Biotechnology, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Hamid Forootanfar

  4. Department of Medicinal Chemistry, Faculty of Pharmacy, Kerman University of Medical Sciences, Kerman, Iran

    Mostafa Pournamdari

  5. Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

    Meysam Ahmadi-Zeidabadi & Marzie Esmaeeli

Authors
  1. Soodeh Salarpour
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  2. Hamid Forootanfar
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  3. Mostafa Pournamdari
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  4. Meysam Ahmadi-Zeidabadi
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  6. Abbas Pardakhty
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Correspondence to Hamid Forootanfar or Abbas Pardakhty.

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High lights

Exosomes were isolated from glioblastoma cells and paclitaxel was loaded in exosomes through two methods of loading: incubation and sonication; cell viability of U-87 cells was significantly decreased by exosomes containing paclitaxel.

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Salarpour, S., Forootanfar, H., Pournamdari, M. et al. Paclitaxel incorporated exosomes derived from glioblastoma cells: comparative study of two loading techniques. DARU J Pharm Sci 27, 533–539 (2019). https://doi.org/10.1007/s40199-019-00280-5

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  • DOI: https://doi.org/10.1007/s40199-019-00280-5

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