JBNB  Vol.2 No.5 , December 2011
A New Biological Strategy for Drug Delivery: Eucaryotic Cell-Derived Nanovesicles
ABSTRACT
An efficient drug delivery is the prerequisite of the successful chemotherapeutic treatments of many human diseases. Despite a great number of approaches, the improvement of drug cell internalization remains an actual research challenge. We propose a new biological delivery system based on the extracellular vesicles released by a non-pathological eukaryotic microorganism, Dictyostelium discoideum. After a summary of the main characteristics of these extracellular vesicles, including of their lipid bilayer that appears as a good candidate for initiating membrane fusion, followed by delivery of their encapsulated drug, the capacity of these vesicles to convey drugs into human cells was demonstrated in vitro on two tumor cell lines, resistant leukaemia K562r and cervix carcinoma HeLa cells. A comparison with other extracellular vesicles, like exosomes or bacteria-derived particles, stresses the unique properties of Dictyostelium extracellular nanovesicles for drug delivery.

Cite this paper
nullTatischeff, I. and Alfsen, A. (2011) A New Biological Strategy for Drug Delivery: Eucaryotic Cell-Derived Nanovesicles. Journal of Biomaterials and Nanobiotechnology, 2, 494-499. doi: 10.4236/jbnb.2011.225060.
References
[1]   W. M. Pardridge, “Molecular Trojan Horses for Blood-Brain Barrier Drug Delivery,” Current Opinion in Pharmacology, Vol. 6, No. 5, 2006, pp. 494-500. doi:10.1016/j.coph.2006.06.001

[2]   Y. Seow and M. J. Wood, “Biological Gene Delivery Vehicles: Beyond Viral Vectors,” The American Society of Gene Therapy, Vol. 17, No. 5, 2009, pp. 767-777.

[3]   K. M. Kroeger, A. K. M. G. Muhammad, G. J. Baker, H. Assi, M. K. Wibowo, W. Xiong, K. Yagiz, M. Candolfi, P. R. Lowenstein and M. G. Castro, “Gene Therapy and Virotherapy: Novel Therapeutic Approaches for Brain Tumors,” Discovery Medicine, Vol. 10, No. 53, 2010, pp. 293-304.

[4]   A. Villaverde, “Nanotechnology, Bionanotechnology and Microbial Cell Factories,” Microbial Cell Factories, Vol. 9, 2010, pp. 53-56. doi:10.1186/1475-2859-9-53

[5]   I. Tatischeff, F. Lavialle, C. de Paillerets, H. Weintraub, G. Tham and A. Alfsen, “Carcinogenic Benzo(a)pyrene and Non-Carcinogenic Benzo(e)pyrene Discriminated by Dictyostelium discoideum Cells Through Internalization,” In: P. Garrigues and M. Lamotte, Eds., Polycyclic Aromatic Compounds, PAH XIII, Gordon and Breach Science Publishers, Switzerland, 1993, pp. 695-702.

[6]   I. Tatischeff and F. Lavialle, “Immunological Evidence of a P-Glycoprotein in the Microorganism Dictyostelium,” Comptes Rendus de l'Académie des Sciences III (Paris), Vol. 316, No. 6, 1993, pp. 560-563.

[7]   I. Tatischeff, M. Bomsel, C. de Paillerets, H. Durand, B. Geny, D. Segretain, E. Turpin and A. Alfsen, “Dictyostelium discoideum Cells Shed Vesicles with Associated DNA and Vital Stain Hoechst 33342,” Cellular and Molecular Life Sciences, Vol. 54, No. 5, 1998, pp. 476-487. doi:10.1007/s000180050176

[8]   I. Tatischeff, F. Lavialle, S. Pigaglio-Deshayes, C. Péchoux-Longin, L. Chinsky and A. Alfsen, “Dictyostelium Extracellular Vesicles Containing Hoechst 33342 Transfer the Dye into the Nuclei of Living Cells: a Fluorescence Study,” Journal of Fluorescence, Vol. 18, No. 2, 2008, pp. 319-328. doi:10.1007/s10895-007-0271-4

[9]   F. Lavialle, S. Deshayes, F. Gonnet, E. Larquet, S. G. Kruglik, N. Boisset, R. Daniel, A. Alfsen and I. Tatischeff, “Nanovesicles Released by Dictyostelium Cells: a Potential Carrier for Drug Delivery,” International Journal of Pharmaceutics, Vol. 380, No. 1-2, 2009, pp. 206-215. doi:10.1016/j.ijpharm.2009.06.039

[10]   D. J. Watts and M. Ashworth, “Growth of Myxameobae of the Cellular Slime Mould Dictyostelium discoideum in Axenic Culture,” Biochemical Journal, Vol. 119, No. 2, 1970, pp. 71-174.

[11]   J. Gruenberg, “Lipids in Endocytic Membrane Transport and Sorting,” Current Opinion in Cell Biology, Vol. 15, No. 4, 2003, pp. 382-388. doi:10.1016/S0955-0674(03)00078-4

[12]   T. Kobayashi, K. Startchev, A. J. Whitney and J. Gruenberg, “Localization of Lysobisphosphatidic Acid-Rich Membrane Domains in Late Endosomes,” Biological Chemistry, Vol. 382, No. 3, 2001, pp. 483-485. doi:10.1515/BC.2001.059

[13]   T. Kobayashi, M. H. Beuchat, J. Chevallier, A. Makino, N. Mayran, J. M. Escola, C. Lebrand, P. Cosson, T. Kobayashi and J. Gruenberg, “Separation and Characterization of Late Endosomal Membrane Domains,” Journal of Biological Chemistry, Vol. 277, No. 35, 2002, pp. 32157- 32164. doi:10.1074/jbc.M202838200

[14]   C. Yorikawa, H. Shibata, S. Waguri, K. Hatta, M. Horii, K. Katoh, T. Kobayashi, Y. Uchiyama and M. Maki, “Human CHMP6, a Myristoylated ESCRT-III Protein, Interacts Directly with an ESCRT-II Component EAP20 and Regulates Endosomal Cargo Sorting,” Biochemical Journal, Vol. 387, No. 1, 2005, pp. 17-26. doi:10.1042/BJ20041227

[15]   B. Hugel, M. C. Martínez, C. Kunzelmann and J. M. Freyssinet, “Membrane Microparticles: Two Sides of the Coin,” Physiology, Vol. 20, 2005, pp. 22-27. doi:10.1152/physiol.00029.2004

[16]   H. F. G. Heijnen, A. E. Schiel, R. Fijnheer, H. J. Geuze and J. J. Sixma, “Activated Platelets Release Two Types of Membrane Vesicles: Microvesicles by Surface Shedding and Exosomes Derived from Exocytosis of Multivesicular Bodies and Alpha-Granules,” Blood, Vol. 94, No. 11, 1999, pp. 3791-3799.

[17]   K. Denzer, M. van Eijk, M. J. Kleijmeer, E. Akobson, C. de Groot and H. J. Geuze, “Follicular Dendritic Cells Carry MHC Class II-Expressing Microvesicles at their Surface,” The Journal of Immunology, Vol. 165, No. 3, 2000, pp. 1259-1265.

[18]   G. Van Niel, G. Raposo, C. Candalh, M. Boussac, R. Hershberg, N. Cerf-Bensussan and M. Heyman, “Intestinal Epithelial Cells Secrete Exosome-Like Vesicles,” Gastroenterology, Vol. 121, No. 2, 2001, pp. 337-349. doi:10.1053/gast.2001.26263

[19]   B. Fevrier and G. Raposo, “Exosomes: Endosomal-Derived Vesicles Shipping Extracellular Messages,” Current Opinion in Cell Biology, Vol. 16, No. 4, 2004, pp. 415- 421. doi:10.1016/j.ceb.2004.06.003

[20]   L. Chernomordik, M. M. Kozlov and J. Zimmerberg, “Lipids in Biological Membrane Fusion,” The Journal of Membrane Biology, Vol. 146, No.1, 1995, pp. 1-14. doi:10.1007/BF00232676

[21]   M. P. Wymann and R. Schneiter, “Lipid Signalling in Disease,” Nature Reviews Molecular Cell Biology, Vol. 9, No. 2, 2008, pp. 162-176. doi:10.1038/nrm2335

[22]   K. Denzer, M. J. Kleijmeer, H. F. G. Heijnen, W. Stoorvogel and H. J. Geuze, “Exosome: From Internal Vesicle of the Multivesicular Body to Intercellular Signaling Device,” Journal of Cell Science, Vol. 113, No. 19, 2000, pp. 3365-3374.

[23]   A. Delcayre and J. B. Le Pecq, “Exosomes as Novel Therapeutic Nanodevices,” Current Opinion in Molecular Therapy, Vol. 8, No. 1, 2006, pp. 31-38.

[24]   S. Lakhal and M. J. Wood, “Exosome Nanotechnology: an Emerging Paradigm Shift in Drug Delivery: Exploitation of Exosome Nanovesicles for Systemic in Vivo Delivery of RNAi Heralds New Horizons for Drug Delivery across Biological Barriers,” Bioessays, Vol. 33, No. 10, 2011, pp. 737-741. doi:10.1002/bies.201100076

[25]   J. A. MacDiarmid, N. B. Mugridge, J. C. Weiss, L. Phillips, A. L. Burn, R. P. Paulin, J. E. Haasdyk, K. A. Dickson, V. N. Brahmbhatt, S. T. Pattison, A. C. James, G. Al Bakri, R. C. Straw, B. Stillman, R. M. Graham and H. Brahmbhatt, “Bacterially Derived 400 Nm Particles for Encapsulation and Cancer Cell Targeting of Chemotherapeutics,” Cancer Cell, Vol. 11, No. 5, 2007, pp. 431-445. doi:10.1016/j.ccr.2007.03.012

[26]   R. Valenti, V. Huber, M. Iero, P. Filipazzi, G. Parmiani and L. Rivoltini, “Tumor-Released Microvesicles as Vehicles of Immunosuppression,” Cancer Research, Vol. 67, No. 7, 2007, pp. 2912-2915. doi:10.1158/0008-5472.CAN-07-0520

[27]   C. Bies, C. M. Lehr and J. F. Woodley, “Lectin-Mediated Drug Targeting: History and Applications,” Advanced Drug Delivery Reviews, Vol. 56, No. 4, 2004, pp. 425- 435. doi:10.1016/j.addr.2003.10.030

[28]   C. Wilhelm, F. Lavialle, C. Péchoux, I. Tatischeff and F. Gazeau, “Intracellular Trafficking of Magnetic Nanoparticles to Design Multifunctional Biovesicles,” Small, Vol. 4, No. 5, 2008, pp. 577-582. doi:10.1002/smll.200700523

[29]   Y. Lu, J. C. Knol, M. H. K. Linskens, K. Friehs, P. J. M. Van Haastert and E. Flaschel, “Production of the Soluble Human Fas Ligand by Dictyostelium discoideum Cultivated on a Synthetic Medium,” Journal of Biotechnology, Vol. 108, No. 3, 2004, pp. 243-251. doi:10.1016/j.jbiotec.2003.12.006

 
 
Top