Gene therapy is a new kind of medicine, which uses genes as drugs in order to treat life threatening diseases. In the present work, a nonviral vector, aminated β-cyclodextrin-modified-carboxylated magnetic cobalt/nanocellulose composite (ACDC-Co/NCC), was synthesized for efficient transfection of genes into tumour cells. The synthesized ACDC-Co/NCC was characterized by means of FTIR, XRD, SEM, and ESR techniques. DNA condensing ability of ACDC-Co/NCC was found to be increased with increase in amount of ACDC-Co/NCC and 84.9% of DNA (1.0？μg/mL) inclusion was observed with 6.0？μg/mL of ACDC-Co/NCC. The cytotoxicity of ACDC-Co/NCC was observed to be minimal, even at higher concentration, with respect to the model transfecting agent, poly(ethyleneimine) (PEI). 88.2% of the gene was transfected at high dose of DNA, as indicated by the highest luciferase expression. These results indicated that ACDC-Co/NCC might be a promising candidate for gene delivery with the characteristics of good biocompatibility, potential biodegradability, minimal cytotoxicity, and relatively high gene transfection efficiency. 1. Introduction Gene delivery, the incorporation of foreign DNA particles into the host cells, is considered as one of the major objectives in the development of nucleic acid therapeutics. Gene therapy is a suitable substitute for conventional protein therapy because the problems such as bioavailability, systemic toxicity, manufacturing cost, and in vivo clearance rate can be solved [1]. It offers the opportunities and potential to cure both genetic and acquired diseases, such as hemophilia, cystic fibrosis, and cancers [2]. Previous experiments have confirmed that, at the molecular level, cancer is due to defects in the cellular DNA. The molecular pathogenesis of human cancer is due to structural and/or functional alterations of specific genes whose normal function is to control cell birth and cell death [3]. Gene delivery can be mediated by viral and nonviral methods. In viral methods, viruses deliver genetic materials to the specific disease sites via their efficient inherent mechanism. Viral vectors can provide efficient transduction and high gene expression. However, the use of viral vectors is quite limited due to safety concerns such as production of immunogenic reactions or mutagenesis of transfected cells [4]. These have necessitated the design of nonviral vectors as potential alternative which produces less complexity. Nonviral vectors are attractive gene delivery systems for tumour gene therapy [5]. These have low immunogenicity, are easier to
References
[1]
S. Y. Wong, J. M. Pelet, and D. Putnam, “Polymer systems for gene delivery-past, present, and future,” Progress in Polymer Science, vol. 32, no. 8-9, pp. 799–837, 2007.
[2]
T. J. Anchordoquy, S. D. Allison, M. D. C. Molina, L. G. Girouard, and T. K. Carson, “Physical stabilization of DNA-based therapeutics,” Drug Discovery Today, vol. 6, no. 9, pp. 463–470, 2001.
[3]
R. Bernards and R. A. Weinberg, “A progression puzzle,” Nature, vol. 418, no. 6900, p. 823, 2002.
[4]
K. Pal, A. K. Banthia, and D. K. Majumdar, “Polymeric hydrogels: characterization and biomedical applications—a mini review,” Designed Monomers and Polymers, vol. 12, no. 3, pp. 197–220, 2009.
[5]
C. Zhang, S. Gao, W. Jiang et al., “Targeted minicircle DNA delivery using folate-poly(ethylene glycol)-polyethylenimine as non-viral vector,” Biomaterials, vol. 31, pp. 6075–6086, 2010.
[6]
M. Eng and A. Elkordy, “Gene delivery using non-viral vectors (cyclodextrins) with Pluronic-F127 and folic acid,” in Proceedings of the 2nd Electronic Conference on Pharmaceutical Sciences, Sciforum Electronic Conferences Series, pp. 1–39, 2012.
[7]
J. S. Choi and J. S. Park, “Design elements of polymeric gene carrier,” in Biomaterials for Delivery and Targeting of Proteins and Nucleic Acids, R. Mahato, Ed., CRC Press, Boca Raton, Fla, USA, 2005.
[8]
L. De Laporte, J. Cruz Rea, and L. D. Shea, “Design of modular non-viral gene therapy vectors,” Biomaterials, vol. 27, no. 7, pp. 947–954, 2006.
[9]
H. Lv, S. Zhang, B. Wang, S. Cui, and J. Yan, “Toxicity of cationic lipids and cationic polymers in gene delivery,” Journal of Controlled Release, vol. 114, no. 1, pp. 100–109, 2006.
[10]
D. Putnam, “Polymers for gene delivery across length scales,” Nature Materials, vol. 5, no. 6, pp. 439–451, 2006.
[11]
M. A. Mintzer and E. E. Simanek, “Nonviral vectors for gene delivery,” Chemical Reviews, vol. 109, no. 2, pp. 259–302, 2009.
[12]
G. P. Tang, H. Y. Guo, F. Alexis et al., “Low molecular weight polyethylenimines linked by β-cyclodextrin for gene transfer into the nervous system,” Journal of Gene Medicine, vol. 8, no. 6, pp. 736–744, 2006.
[13]
V. Burckbuchler, V. Wintgens, C. Leborgne et al., “Development and characterization of new cyclodextrin polymer-based DNA delivery systems,” Bioconjugate Chemistry, vol. 19, no. 12, pp. 2311–2320, 2008.
[14]
A. Rasheed, A. Kumar, and V. V. N. S. S. Sravanthi, “Cyclodextrins as drug carrier molecule: a review,” Scientia Pharmaceutica, vol. 76, no. 4, pp. 567–598, 2008.
[15]
S. C. McBain, H. H. P. Yiu, A. El Haj, and J. Dobson, “Polyethyleneimine functionalized iron oxide nanoparticles as agents for DNA delivery and transfection,” Journal of Materials Chemistry, vol. 17, no. 24, pp. 2561–2565, 2007.
[16]
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.
[17]
E. M. Umut, Surface Modification of Nanoparticles Used in Biomedical Applications, InTech, 2013.
[18]
S. Liang, Y. Wang, C. Zhang et al., “Synthesis of amino-modified magnetite nanoparticles coated with Hepama-1 and radiolabeled with 188Re for bio-magnetically targeted radiotherapy,” Journal of Radioanalytical and Nuclear Chemistry, vol. 269, no. 1, pp. 3–7, 2006.
[19]
M. A. McDonald and K. L. Watkin, “Investigations into the physicochemical properties of dextran small particulate gadolinium oxide nanoparticles,” Academic Radiology, vol. 13, no. 4, pp. 421–427, 2006.
[20]
T. Heinze, T. Liebert, B. Heublein, and S. Hornig, “Functional polymers based on dextran,” Advances in Polymer Science, vol. 205, no. 1, pp. 199–291, 2006.
[21]
T. Maneerung, S. Tokura, and R. Rujiravanit, “Impregnation of silver nanoparticles into bacterial cellulose for antimicrobial wound dressing,” Carbohydrate Polymers, vol. 72, no. 1, pp. 43–51, 2008.
[22]
J. Cai, S. Kimura, M. Wada, and S. Kuga, “Nanoporous cellulose as metal nanoparticles support,” Biomacromolecules, vol. 10, no. 1, pp. 87–94, 2009.
[23]
E. Lam, K. B. Male, J. H. Chong, A. C. W. Leung, and J. H. T. Luong, “Applications of functionalized and nanoparticle-modified nanocrystalline cellulose,” Trends in Biotechnology, vol. 30, no. 5, pp. 283–290, 2012.
[24]
J. Vadolas, R. Williamson, and P. A. Ioannou, “Gene therapy for inherited lung disorders: an insight into pulmonary defence,” Pulmonary Pharmacology and Therapeutics, vol. 15, no. 1, pp. 61–72, 2002.
[25]
Z. Mohammadi, M. Abolhassani, F. A. Dorkoosh et al., “Preparation and evaluation of chitosan-DNA-FAP-B nanoparticles as a novel non-viral vector for gene delivery to the lung epithelial cells,” International Journal of Pharmaceutics, vol. 409, no. 1-2, pp. 307–313, 2011.
[26]
S. W. Gersting, U. Schillinger, J. Lausier et al., “Gene delivery to respiratory epithelial cells by magnetofection,” Journal of Gene Medicine, vol. 6, no. 8, pp. 913–922, 2004.
[27]
F. Kr？tz, H.-Y. Sohn, T. Gloe, C. Plank, and U. Pohl, “Magnetofection potentiates gene delivery to cultured endothelial cells,” Journal of Vascular Research, vol. 40, no. 5, pp. 425–434, 2003.
[28]
S. C. McBain, H. H. P. Yiu, and J. Dobson, “Magnetic nanoparticles for gene and drug delivery,” International Journal of Nanomedicine, vol. 3, no. 2, pp. 169–180, 2008.
[29]
B. Abdallah, A. Hassan, C. Benoist, D. Goula, J. P. Behr, and B. A. Demeneix, “A powerful nonviral vector for in vivo gene transfer into the adult mammalian brain: polyethylenimine,” Human Gene Therapy, vol. 7, no. 16, pp. 1947–1954, 1996.
[30]
T. S. Anirudhan and S. R. Rejeena, “Adsorption and hydrolytic activity of trypsin on a carboxylate-functionalized cation exchanger prepared from nanocellulose,” Journal of Colloid and Interface Science, vol. 381, no. 1, pp. 125–136, 2012.
[31]
D. R. Mulinari and M. L. C. P. da Silva, “Adsorption of sulphate ions by modification of sugarcane bagasse cellulose,” Carbohydrate Polymers, vol. 74, no. 3, pp. 617–620, 2008.
[32]
J. R. Capadona, K. Shanmuganathan, S. Trittschuh, S. Seidel, S. J. Rowan, and C. Weder, “Polymer nanocomposites with nanowhiskers isolated from microcrystalline cellulose,” Biomacromolecules, vol. 10, no. 4, pp. 712–716, 2009.
[33]
J. Araki, M. Wada, and S. Kuga, “Steric stabilization of a cellulose microcrystal suspension by poly(ethylene glycol) grafting,” Langmuir, vol. 17, no. 1, pp. 21–27, 2001.
[34]
R. C. Petter, J. S. Salek, C. T. Sikorski, G. Kumaravel, and F.-T. Lin, “Cooperative binding by aggregated mono-6-(alkylamino)-β-cyclodextrins,” Journal of the American Chemical Society, vol. 112, no. 10, pp. 3860–3868, 1990.
[35]
X. Zhang, Z. Wu, X. Gao et al., “Chitosan bearing pendant cyclodextrin as a carrier for controlled protein release,” Carbohydrate Polymers, vol. 77, no. 2, pp. 394–401, 2009.
[36]
N. Aoki, M. Nishikawa, and K. Hattori, “Synthesis of chitosan derivatives bearing cyclodextrin and adsorption of p-nonylphenol and bisphenol A,” Carbohydrate Polymers, vol. 52, no. 3, pp. 219–223, 2003.
[37]
I. G. Shibi and T. S. Anirudhan, “Synthesis, characterization, and application as a mercury(II) sorbent of banana stalk (Musa paradisiaca)—polyacrylamide grafted copolymer bearing carboxyl groups,” Industrial and Engineering Chemistry Research, vol. 41, no. 22, pp. 5341–5352, 2002.
[38]
W.-F. Lai, G.-P. Tang, X. Wang et al., “Cyclodextrin-PEI-Tat polymer as a vector for plasmid DNA delivery to placenta mesenchymal stem cells,” BioNanoScience, vol. 1, no. 3, pp. 89–96, 2011.
[39]
L. V. A. Gurgel, O. K. Júnior, R. P. D. F. Gil, and L. F. Gil, “Adsorption of Cu(II), Cd(II), and Pb(II) from aqueous single metal solutions by cellulose and mercerized cellulose chemically modified with succinic anhydride,” Bioresource Technology, vol. 99, no. 8, pp. 3077–3083, 2008.
[40]
A. Alemdar and M. Sain, “Isolation and characterization of nanofibers from agricultural residues—wheat straw and soy hulls,” Bioresource Technology, vol. 99, no. 6, pp. 1664–1671, 2008.
[41]
K. Das, D. Ray, C. Banerjee et al., “Physicomechanical and thermal properties of jute-nanofiber-reinforced biocopolyester composites,” Industrial and Engineering Chemistry Research, vol. 49, no. 6, pp. 2775–2782, 2010.
[42]
P. Scherrer, “Bestimmung der Gr？sse und der inneren Struktur von Kolloidteilchen mittels R？ntgenstrahlen,” Nachrichten von der Gesellschaft der Wissenschaften zu Gottingen, vol. 26, pp. 98–100, 1918.
[43]
G. Bayramo？lu, M. Yilmaz, A. ü. ？enel, and M. Y. Arica, “Preparation of nanofibrous polymer grafted magnetic poly(GMA-MMA)-g-MAA beads for immobilization of trypsin via adsorption,” Biochemical Engineering Journal, vol. 40, no. 2, pp. 262–274, 2008.
[44]
D. Fischer, T. Bieber, Y. Li, H.-P. Els？sser, 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.
[45]
B. Liang, M.-L. He, Z.-P. Xiao et al., “Synthesis and characterization of folate-PEG-grafted-hyperbranched-PEI for tumor-targeted gene delivery,” Biochemical and Biophysical Research Communications, vol. 367, no. 4, pp. 874–880, 2008.
