Table of Contents Author Guidelines Submit a Manuscript
Journal of Drug Delivery
Volume 2012, Article ID 218940, 12 pages
http://dx.doi.org/10.1155/2012/218940
Research Article

Intracellular Delivery of siRNA by Polycationic Superparamagnetic Nanoparticles

1Department of Chemistry, University of Puerto Rico at Humacao, Humacao 00791, Puerto Rico
2Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge University, MA 02139, USA
3Department of Biology, University of Puerto Rico at Río Piedras, San Juan 00931, Puerto Rico

Received 15 February 2012; Revised 11 July 2012; Accepted 14 July 2012

Academic Editor: Indu Pal Kaur

Copyright © 2012 Betzaida Castillo et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. S. W. Jones, P. M. de Souza, and M. M. A. Lindsay, “siRNA for gene silencing: a route to drug target discovery,” Current Opinion in Pharmacology, vol. 4, no. 5, pp. 522–527, 2004. View at Publisher · View at Google Scholar · View at Scopus
  2. T. Tokatlian and T. Segura, “siRNA applications in nanomedicine,” Nanomedicine and Nanobiotechnology, vol. 2, no. 3, pp. 305–315, 2010. View at Publisher · View at Google Scholar · View at Scopus
  3. M. M. Fabani, J. J. Turner, and M. J. Gait, “Oligonucleotide analogs as antiviral agents,” Current Opinion in Molecular Therapeutics, vol. 8, no. 2, pp. 108–114, 2006. View at Google Scholar · View at Scopus
  4. M. Masiero, G. Nardo, S. Indraccolo, and E. Favaro, “RNA interference: implications for cancer treatment,” Molecular Aspects of Medicine, vol. 28, no. 1, pp. 143–166, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. B. K. Biswal, N. B. Debata, and R. S. Verma, “Development of a targeted siRNA delivery system using FOL-PEG-PEI conjugate,” Molecular Biology Reports, vol. 37, no. 6, pp. 2919–2926, 2010. View at Publisher · View at Google Scholar · View at Scopus
  6. A. Beyerle, O. Merkel, T. Stoeger, and T. Kissel, “PEGylation affects cytotoxicity and cell-compatibility of poly(ethylene imine) for lung application: structure-function relationships,” Toxicology and Applied Pharmacology, vol. 242, no. 2, pp. 146–154, 2010. View at Publisher · View at Google Scholar · View at Scopus
  7. S. H. Kim, J. H. Jeong, S. H. Lee, S. W. Kim, and T. G. Park, “PEG conjugated VEGF siRNA for anti-angiogenic gene therapy,” Journal of Controlled Release, vol. 116, no. 2, pp. 123–129, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. S. L. Bøe, A. S. Longva, and E. Hovig, “Cyclodextrin-containing polymer delivery system for Light-Directed siRNA gene silencing,” Oligonucleotides, vol. 20, no. 4, pp. 175–182, 2010. View at Publisher · View at Google Scholar · View at Scopus
  9. H. Song and P. C. Yang, “Construction of shRNA lentiviral vector,” North American Journal of Medical Sciences, vol. 2, pp. 598–601, 2010. View at Google Scholar
  10. S. Höbel and A. Aigner, “Polyethylenimine (PEI)/siRNA-mediated gene knockdown in vitro and in vivo,” Methods in Molecular Biology, vol. 623, pp. 283–297, 2010. View at Publisher · View at Google Scholar · View at Scopus
  11. J. Guo, L. Bourre, D. M. Soden, G. C. O'Sullivan, and C. O'Driscoll, “Can non-viral technologies knockdown the barriers to siRNA delivery and achieve the next generation of cancer therapeutics?” Biotechnology Advances, vol. 29, no. 4, pp. 402–417, 2011. View at Publisher · View at Google Scholar · View at Scopus
  12. M. Thomas, J. J. Lu, Q. Ge, C. Zhang, J. Chen, and A. M. Klibanov, “Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 16, pp. 5679–5684, 2005. View at Publisher · View at Google Scholar · View at Scopus
  13. A. E. Felber, B. Castagner, M. Elsabahy, G. F. Deleavey, M. J. Damha, and J. C. Leroux, “SiRNA nanocarriers based on methacrylic acid copolymers,” Journal of Controlled Release, vol. 152, no. 1, pp. 159–167, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. V. Deleuze, E. Chalhoub, R. El-Hajj et al., “TAL-1/SCL and its partners E47 and LMO2 up-regulate VE-cadherin expression in endothelial cells,” Molecular and Cellular Biology, vol. 27, no. 7, pp. 2687–2697, 2007. View at Publisher · View at Google Scholar · View at Scopus
  15. M. Doshida, M. Ohmichi, S. Tsutsumi et al., “Raloxifene increases proliferation and up-regulates telomerase activity in human umbilical vein endothelial cells,” Journal of Biological Chemistry, vol. 281, no. 34, pp. 24270–24278, 2006. View at Publisher · View at Google Scholar · View at Scopus
  16. P. Huang, T. Senga, and M. Hamaguchi, “A novel role of phospho-β-catenin in microtubule regrowth at centrosome,” Oncogene, vol. 26, no. 30, pp. 4357–4371, 2007. View at Publisher · View at Google Scholar · View at Scopus
  17. R. Ensenauer, D. Hartl, J. Vockley, A. A. Roscher, and U. Fuchs, “Efficient and gentle siRNA delivery by magnetofection,” Biotechnic and Histochemistry, vol. 86, no. 4, pp. 226–231, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. Y. Shi, L. Zhou, R. Wang et al., “In situ preparation of magnetic nonviral gene vectors and magnetofection in vitro,” Nanotechnology, vol. 21, no. 11, p. 115103, 2010. View at Publisher · View at Google Scholar · View at Scopus
  19. O. Mykhaylyk, O. Zelphati, J. Rosenecker, and C. Plank, “siRNA delivery by magnetofection,” Current Opinion in Molecular Therapeutics, vol. 10, no. 5, pp. 493–505, 2008. View at Google Scholar · View at Scopus
  20. C. Plank, U. Schillinger, F. Scherer et al., “The magnetofection method: using magnetic force to enhance gene delivery,” Biological Chemistry, vol. 384, no. 5, pp. 737–747, 2003. View at Publisher · View at Google Scholar · View at Scopus
  21. C. Plank, M. Anton, C. Rudolph, J. Rosenecker, and F. Krötz, “Enhancing and targeting nucleic acid delivery by magnetic force,” Expert Opinion on Biological Therapy, vol. 3, no. 5, pp. 745–758, 2003. View at Publisher · View at Google Scholar · View at Scopus
  22. O. Mykhaylyk, Y. S. Antequera, D. Vlaskou, and C. Plank, “Generation of magnetic nonviral gene transfer agents and magnetofection in vitro,” Nature protocols, vol. 2, no. 10, pp. 2391–2411, 2007. View at Publisher · View at Google Scholar · View at Scopus
  23. F. Krötz, C. de Wit, H. Y. Sohn et al., “Magnetofection—a highly efficient tool for antisense oligonucleotide delivery in vitro and in vivo,” Molecular Therapy, vol. 7, no. 5, pp. 700–710, 2003. View at Publisher · View at Google Scholar · View at Scopus
  24. F. Scherer, M. Anton, U. Schillinger et al., “Magnetofection: enhancing and targeting gene delivery by magnetic force in vitro and in vivo,” Gene Therapy, vol. 9, no. 2, pp. 102–109, 2002. View at Publisher · View at Google Scholar · View at Scopus
  25. O. Mykhaylyk, D. Vlaskou, N. Tresilwised, P. Pithayanukul, W. Möller, and C. Plank, “Magnetic nanoparticle formulations for DNA and siRNA delivery,” Journal of Magnetism and Magnetic Materials, vol. 311, no. 1, pp. 275–281, 2007. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Schlorf, M. Meincke, E. Kossel, C. C. Glüer, O. Jansen, and R. Mentlein, “Biological properties of iron oxide nanoparticles for cellular and molecular magnetic resonance imaging,” International Journal of Molecular Sciences, vol. 12, no. 1, pp. 12–23, 2011. View at Publisher · View at Google Scholar · View at Scopus
  27. S. M. Griffiths, N. Singh, G. J. S. Jenkins et al., “Dextran coated ultrafine superparamagnetic iron oxide nanoparticles: compatibility with common fluorometric and colorimetric dyes,” Analytical Chemistry, vol. 83, no. 10, pp. 3778–3785, 2011. View at Publisher · View at Google Scholar · View at Scopus
  28. B. A. Katsnelson, T. D. Degtyareva, I. I. Minigalieva et al., “Subchronic systemic toxicity and bioaccumulation of Fe3O4 nano- and microparticles following repeated intraperitoneal administration to rats,” International Journal of Toxicology, vol. 30, no. 1, pp. 59–68, 2011. View at Publisher · View at Google Scholar · View at Scopus
  29. L. Bromberg, E. P. Chang, T. A. Hatton, A. Concheiro, B. Magariños, and C. Alvarez-Lorenzo, “Bactericidal core-shell paramagnetic nanoparticles functionalized with poly(hexamethylene biguanide),” Langmuir, vol. 27, no. 1, pp. 420–429, 2011. View at Publisher · View at Google Scholar · View at Scopus
  30. N. A. Frey, S. Peng, K. Cheng, and S. Sun, “Magnetic nanoparticles: synthesis, functionalization, and applications in bioimaging and magnetic energy storage,” Chemical Society Reviews, vol. 38, no. 9, pp. 2532–2542, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. P. Tartaj, M. Del Puerto Morales, S. Veintemillas-Verdaguer, T. González-Carreño, and C. J. Serna, “The preparation of magnetic nanoparticles for applications in biomedicine,” Journal of Physics D, vol. 36, no. 13, pp. R182–R197, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. S. R. Bhattarai, S. Y. Kim, K. Y. Jang et al., “N-hexanoyl chitosan-stabilized magnetic nanoparticles: enhancement of adenoviral-mediated gene expression both in vitro and in vivo,” Nanomedicine, vol. 4, no. 2, pp. 146–154, 2008. View at Publisher · View at Google Scholar · View at Scopus
  33. R. Weissleder, D. D. Stark, B. L. Engelstad et al., “Superparamagnetic iron oxide: pharmacokinetics and toxicity,” American Journal of Roentgenology, vol. 152, no. 1, pp. 167–173, 1989. View at Google Scholar · View at Scopus
  34. A. S. Arbab, L. B. Wilson, P. Ashari, E. K. Jordan, B. K. Lewis, and J. A. Frank, “A model of lysosomal metabolism of dextran coated superparamagnetic iron oxide (SPIO) nanoparticles: implications for cellular magnetic resonance imaging,” NMR in Biomedicine, vol. 18, no. 6, pp. 383–389, 2005. View at Publisher · View at Google Scholar · View at Scopus
  35. E. Pawelczyk, A. S. Arbab, S. Pandit, E. Hu, and J. A. Frank, “Expression of transferrin receptor and ferritin following ferumoxides-protamine sulfate labeling of cells: implications for cellular magnetic resonance imaging,” NMR in Biomedicine, vol. 19, no. 5, pp. 581–592, 2006. View at Publisher · View at Google Scholar · View at Scopus
  36. C. Plank, O. Zelphati, and O. Mykhaylyk, “Magnetically enhanced nucleic acid delivery. Ten years of magnetofection-Progress and prospects,” Advanced Drug Delivery Reviews, vol. 63, pp. 1300–1331, 2011. View at Google Scholar
  37. A. C. Richards Grayson, A. M. Doody, and D. Putnam, “Biophysical and structural characterization of polyethylenimine-mediated siRNA delivery in vitro,” Pharmaceutical Research, vol. 23, no. 8, pp. 1868–1876, 2006. View at Publisher · View at Google Scholar · View at Scopus
  38. B. Urban-Klein, S. Werth, S. Abuharbeid, F. Czubayko, and A. Aigner, “RNAi-mediated gene-targeting through systemic application of polyethylenimine (PEI)-complexed siRNA in vivo,” Gene Therapy, vol. 12, no. 5, pp. 461–466, 2005. View at Publisher · View at Google Scholar · View at Scopus
  39. M. L. Read, S. Singh, Z. Ahmed et al., “A versatile reducible polycation-based system for efficient delivery of a broad range of nucleic acids,” Nucleic Acids Research, vol. 33, no. 9, article e86, 2005. View at Google Scholar · View at Scopus
  40. A. Akinc, M. Thomas, A. M. Klibanov, and R. Langer, “Exploring polyethylenimine-mediated DNA transfection and the proton sponge hypothesis,” Journal of Gene Medicine, vol. 7, no. 5, pp. 657–663, 2005. View at Publisher · View at Google Scholar · View at Scopus
  41. M. Grzelinski, B. Urban-Klein, T. Martens et al., “RNA interference-mediated gene silencing of pleiotrophin through polyethylenimine-complexed small interfering RNAs in vivo exerts antitumoral effects in glioblastoma xenografts,” Human Gene Therapy, vol. 17, no. 7, pp. 751–766, 2006. View at Publisher · View at Google Scholar · View at Scopus
  42. Q. Ge, L. Filip, A. Bai, T. Nguyen, H. N. Eisen, and J. Chen, “Inhibition of influenza virus production in virus-infected mice by RNA interference,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 23, pp. 8676–8681, 2004. View at Publisher · View at Google Scholar · View at Scopus
  43. R. M. Schiffelers, A. Ansari, J. Xu et al., “Cancer siRNA therapy by tumor selective delivery with ligand-targeted sterically stabilized nanoparticle,” Nucleic Acids Research, vol. 32, no. 19, article e149, 2004. View at Google Scholar · View at Scopus
  44. M. Thomas, J. J. Lu, Q. Ge, C. Zhang, J. Chen, and A. M. Klibanov, “Full deacylation of polyethylenimine dramatically boosts its gene delivery efficiency and specificity to mouse lung,” Proceedings of the National Academy of Sciences of the United States of America, vol. 102, no. 16, pp. 5679–5684, 2005. View at Publisher · View at Google Scholar · View at Scopus
  45. P. Chollet, M. C. Favrot, A. Hurbin, and J. L. Coll, “Side-effects of a systemic injection of linear polyethylenimine-DNA complexes,” Journal of Gene Medicine, vol. 4, no. 1, pp. 84–91, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. S. Höbel, R. Prinz, A. Malek et al., “Polyethylenimine PEI F25-LMW allows the long-term storage of frozen complexes as fully active reagents in siRNA-mediated gene targeting and DNA delivery,” European Journal of Pharmaceutics and Biopharmaceutics, vol. 70, no. 1, pp. 29–41, 2008. View at Publisher · View at Google Scholar · View at Scopus
  47. D. Fischer, T. Bieber, Y. Li, H. P. Elsässer, and T. Kissel, “A novel non-viral vector for DNA delivery based on low molecular weight, branched polyethylenimine: effect of molecular weight on transfection efficiency and cytotoxicity,” Pharmaceutical Research, vol. 16, no. 8, pp. 1273–1279, 1999. View at Publisher · View at Google Scholar · View at Scopus
  48. W. T. Godbey, K. K. Wu, and A. G. Mikos, “Poly(ethylenimine) and its role in gene delivery,” Journal of Controlled Release, vol. 60, no. 2-3, pp. 149–160, 1999. View at Publisher · View at Google Scholar · View at Scopus
  49. W. T. Kuo, H. Y. Huang, and Y. Y. Huang, “Intracellular trafficking, metabolism and toxicity of current gene carriers,” Current Drug Metabolism, vol. 10, no. 8, pp. 885–894, 2009. View at Publisher · View at Google Scholar · View at Scopus
  50. L. Bromberg, S. Raduyk, and T. A. Hatton, “Functional magnetic nanoparticles for biodefense and biological threat monitoring and surveillance,” Analytical Chemistry, vol. 81, no. 14, pp. 5637–5645, 2009. View at Publisher · View at Google Scholar · View at Scopus
  51. L. Bromberg, E. P. Chang, C. Alvarez-Lorenzo, B. Magariños, A. Concheiro, and T. A. Hatton, “Binding of functionalized paramagnetic nanoparticles to bacterial lipopolysaccharides and DNA,” Langmuir, vol. 26, no. 11, pp. 8829–8835, 2010. View at Publisher · View at Google Scholar · View at Scopus
  52. L. Bromberg, D. J. Bromberg, T. A. Hatton, I. Bandín, A. Concheiro, and C. Alvarez-Lorenzo, “Antiviral properties of polymeric aziridine- and biguanide-modified core−shell magnetic nanoparticles,” Langmuir, vol. 28, pp. 4548–4558, 2012. View at Google Scholar
  53. D. Ang, Q. V. Nguyen, S. Kayal, P. R. Preiser, R. S. Rawat, and R. V. Ramanujan, “Insights into the mechanism of magnetic particle assisted gene delivery,” Acta Biomaterialia, vol. 7, no. 3, pp. 1319–1326, 2011. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Moghimi, P. Symonds, J. C. Murray, A. C. Hunter, G. Debska, and A. Szewczyk, “A two-stage poly(ethylenimine)-mediated cytotoxicity: implications for gene transfer/therapy,” Molecular Therapy, vol. 11, no. 6, pp. 990–995, 2005. View at Publisher · View at Google Scholar · View at Scopus
  55. D. Putnam, C. A. Gentry, D. W. Pack, and R. Langer, “Polymer-based gene delivery with low cytotoxicity by a unique balance of side-chain termini,” Proceedings of the National Academy of Sciences of the United States of America, vol. 98, no. 3, pp. 1200–1205, 2001. View at Publisher · View at Google Scholar · View at Scopus
  56. Y. Fedorov, E. M. Anderson, A. Birmingham et al., “Off-target effects by siRNA can induce toxic phenotype,” RNA, vol. 12, no. 7, pp. 1188–1196, 2006. View at Publisher · View at Google Scholar · View at Scopus
  57. M. Neu, D. Fischer, and T. Kissel, “Recent advances in rational gene transfer vector design based on poly(ethylene imine) and its derivatives,” Journal of Gene Medicine, vol. 7, no. 8, pp. 992–1009, 2005. View at Publisher · View at Google Scholar · View at Scopus
  58. J. A. Fortune, T. I. Novobrantseva, and A. M. Klibanov, “Highly effective gene transfection in vivo by alkylated polyethylenimine,” Journal of Drug Delivery, vol. 2011, Article ID 204058, 6 pages, 2011. View at Publisher · View at Google Scholar
  59. J. F. Tan, T. A. Hatton, K. C. Tam, and H. P. Too, “Correlating transfection barriers and biophysical properties of cationic polymethacrylates,” Biomacromolecules, vol. 8, no. 2, pp. 448–454, 2007. View at Publisher · View at Google Scholar · View at Scopus
  60. S. J. Ryhänen, M. J. Säily, T. Paukku et al., “Surface charge density determines the efficiency of cationic gemini surfactant based lipofection,” Biophysical Journal, vol. 84, no. 1, pp. 578–587, 2003. View at Google Scholar · View at Scopus
  61. L. C. Mounkes, W. Zhong, G. Cipres-Palacin, T. D. Heath, and R. J. Debs, “Proteoglycans mediate cationic liposome-DNA complex-based gene delivery in vitro and in vivo,” Journal of Biological Chemistry, vol. 273, no. 40, pp. 26164–26170, 1998. View at Publisher · View at Google Scholar · View at Scopus
  62. B. L. Ibey, C. C. Roth, A. G. Pakhomov, J. A. Bernhard, G. J. Wilmink, and O. N. Pakhomova, “Dose-dependent thresholds of 10-ns electric pulse induced plasma membrane disruption and cytotoxicity in multiple cell lines,” PLoS ONE, vol. 6, no. 1, Article ID e15642, 2011. View at Publisher · View at Google Scholar · View at Scopus