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Hydrophobically modified chitosan/gold nanoparticles for DNA delivery

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Abstract

Present study dealt an application of modified chitosan gold nanoparticles (Nac-6-Au) for the immobilization of necked plasmid DNA. Gold nanoparticles stabilized with N-acylated chitosan were prepared by graft-onto approach. The stabilized gold nanoparticles were characterized by different physico-chemical techniques such as UV-vis, TEM, ELS and DLS. MTT assay was used for in vitro cytotoxicity of the nanoparticles into three different cell lines (NIH 3T3, CT-26 and MCF-7). The formulation of plasmid DNA with the nanoparticles corresponds to the complex forming capacity and in-vitro/in-vivo transfection efficiency was studied via gel electrophoresis and transfection methods, respectively. Results showed the modified chitosan gold nanoparticles were well-dispersed and spherical in shape with average size around 10∼12 nm in triple distilled water at pH 7.4, and showed relatively no cytotoxicity at low concentration. Addition of plasmid DNA on the aqueous solution of the nanoparticles markedly reduced surface potential (50.0∼66.6%) as well as resulted in a 13.33% increase in hydrodynamic diameters of the formulated nanoparticles. Transfection efficiency of Nac-6-Au/DNA was dependent on cell type, and higher β-galactosidase activity was observed on MCF-7 breast cancer cell. Typically, this activity was 5 times higher in 4.5 mg/ml nanoparticles concentration than that achieved by the nanoparticles of other concentrations (and/or control). However, this activity was lower in in-vitro and dramatically higher in in-vivo than that of commercially available transfection kit (Lipofectin®) and DNA. From these results, it can be expected to develop alternative new vectors for gene delivery.

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References

  • Artursson P, Lindmark T, Davis SS, Illum L (1994) Effect of chitosan on the permeability of monolayers of intestinal epithelial cells (Caco-2). Pharm Res 11:1358–1361

    Article  CAS  Google Scholar 

  • Ana Y, Zhaia P, Dashtia AM, Wua S, Lina X, Wub MA (2002) Combined gene delivery by co-transduction of adenoviral and retroviral vectors for cancer gene therapy. Cancer Lett 184:179–188

    Article  Google Scholar 

  • Aral C, Akbuga J (1999) Preparation and in vitro transfection efficiency of chitosan microspheres containing plasmid DNA: poly (l-lysine) complexes. J Pharm Sci 6:73–82

    Google Scholar 

  • Aryal S, KC RB, Dharmaraj N, Bhattarai N, Kim CH, Kim HY (2006) Spectroscopic identification of S–Au interacton in cysteine capped gold nanoparticles. Spectrochimica Acta Part A 63:160–163

    Article  Google Scholar 

  • Bhattarai N, Bhattarai SR, Yi HK, Lee JC, Khil MS, Hwang PH, Kim HY (2003) Novel polymeric micelles of amphiphilic triblock copolymer poly (p-Dioxanone-co-l-Lactide)-block-Poly (ethylene glycol). Pharm Res 20:2021–2027

    Article  CAS  Google Scholar 

  • Bhattarai SR, Yi HK, Bhattarai N, Hwang PH, Kim HY (2006) Novel block copolymer (PPDO/PLLA-b-PEG): Enhancement of DNA uptake and cell transfection. Acta Biomaterialia 2:207–212

    Article  Google Scholar 

  • Chae SY, Son S, Lee M, Jang MK, Nah JW (2005) Deoxycholic acid-conjugated chitosan oligosaccharide nanoparticles for efficient gene carrier. J Control Release 109:330–334

    Article  CAS  Google Scholar 

  • Corsi K, Chellat F, Yahia H, Fernades JC (2003) Mesenchymal stem cells, MG63 and HEK293 Transfection using chitosan-DNA nanoparticles. Biomaterials 24:1255–1264

    Article  CAS  Google Scholar 

  • Chakrabarti R, Klibanov AM (2003) Nanocrystals modified with peptide nucleic acids (PNAs) for selective self-assembly and DNA detection. J Am Chem Soc 125:12531–12540

    Article  CAS  Google Scholar 

  • Daniel MC, Astruc D (2004) Gold nanoparticles: assembly, supramolecular chemistry, quantum-size-related properties. Chem Rev 104:293–346

    Article  CAS  Google Scholar 

  • Ferrari S, Duncan GM, Alton WFW (2002) Barriers to and new approaches for gene therapy and gene delivery in cystic fibrosis. Adv Drug Delivery Rev 54:1373–1393

    Article  CAS  Google Scholar 

  • Iqbal M, Lin W, Jabbal-Gill I, Davis SS, Steward MW, Illum L (2003) Nasal delivery of chitosan–DNA plasmid expressing epitopes of respiratory syncytial virus (RSV) induces protective CTL responses in BALB/c mice. Vaccine 21:1478–1485

    Article  CAS  Google Scholar 

  • Ishii T, Okahata Y, Sato T (2001) Mechanism of cell transfection with plasmid/chitosan complexes. BBA-Biomembranes 1514:51–64

    Article  CAS  Google Scholar 

  • Kai E, Ochiya T (2004) A method for oral DNA delivery with N-Acetylated Chitosan. Pharm Res 21:838–843

    Article  CAS  Google Scholar 

  • KC RB, Aryal S, Bhattarai SR, Bhattarai N, Kim CH, Kim HY (2006) Stabilization of gold nanoparticles by hydrophobically modified polycations. J Biomater Sci Polym Ed 17(5):576–589

    Google Scholar 

  • Kim TH, Park IK, Nah JW, Choi YJ, Cho CS (2004) Galactosylated chitosan/DNA nanoparticles prepared using water-soluble chitosan as a gene carrier. Biomaterials 25:3783–3792

    Article  CAS  Google Scholar 

  • Koping-Hoggard M, Guan IT, Edwards K, Nilsson M, Varum KM, Artursson P (2001) Chitosan as a nonviral gene delivery system. Structure–property relationships and characteristics compared with polyethylenimine in vitro and after lung administration in vivo. Gene Therapy 8:1108–1121

    Article  CAS  Google Scholar 

  • Kulmeet IS, Catherine MM, Joseph MS, Sallie WS, Vincent MR (2002) Gold nanoparticles mediated transfection of mammalian cells. Bioconjugate Chememistry 13:3–6

    Article  Google Scholar 

  • Lee KY, Kwon IC, Kim YH, Jo WH, Jeong SY (1998) Reparation of chitosan self-aggregates as a gene delivery system. J Control Release 51:213–220

    Article  CAS  Google Scholar 

  • Leong KW, Mao HQ, Truong-Le VL, Roy K, Walsh SM, August JT (1998) DNA-polycation nanospheres as non-viral gene delivery vehicles. J Control Release 53:183–193

    Article  CAS  Google Scholar 

  • Lundstrom K (2003) Latest development in viral vectors for gene therapy. Trends Biotechnol 21:117–122

    Article  CAS  Google Scholar 

  • Le Tien C, Lacroix M, Ispas-Szabo P, Mateescu MA (2003) N-acylated chitosan: hydrophobic matrices for controlled drug release. J Control Release 93:1–13

    Article  CAS  Google Scholar 

  • Maclaughlin FC, Mumper RJ, Wang J et al (1998) Chitosan and de-polymerized chitosan oligomers as condensing carriers for in vivo plasmid deliver. J Control Release 56:259–272

    Article  CAS  Google Scholar 

  • Mao HQ, Roy K, Troung-Le VL, Janes KA et al (2001) Chitosan-DNA nanoparticles as gene carriers: synthesis, characterization and Transfection efficiency. J Control Release 70:399–421

    Article  CAS  Google Scholar 

  • Park IK, Kim TH, Park YH, Shin BA, Choi ES et al (2001) Galactosylated chitosan-graft-poly (ethylene glycol) as hepatocyte-targeting DNA carrier. J Control Release 76:349–362

    Article  CAS  Google Scholar 

  • Pertmer TM, Eisenbraun DM, McCabe D, Prayaga SK, Haynes JR (1995) Gene gun-based nucleic acid immunization: elicitation of humoral and cytotoxic T lymphocyte responses following epidermal delivery of nanogram quantities of DNA. Vaccine 13:1427–1430

    Article  CAS  Google Scholar 

  • Quong D, Yeo JN, Neufeld RJ (1999) Stability of chitosan and poly-l-lysine membrane coating DNA-alginate beads when exposed to hydrolytic enzymes. J Microencapsulation 16:73–82

    Article  CAS  Google Scholar 

  • Quong D, Neufeld R (1998) DNA protection from extracapsular nucleases, within chitosan or poly-l-lysine-coated alginate beads. J Biotechnol Bioeng 60:124–134

    Article  CAS  Google Scholar 

  • Ravi Kumar MNV, Bakowsky U, Lehr CM (2004) Preparation and characterization of cationic PLGA nanospheres as DNA carriers. Biomaterials 25:1771–1777

    Article  CAS  Google Scholar 

  • Roy K, Mao HQ, Huang SK, Leong KW (1999) Oral gene delivery with chitosan-DNA nanoparticles generates immunologic protection in a murine model of peanut allergy. Nature Med 5:387–391

    Article  CAS  Google Scholar 

  • Ruponena M, Honkakoskia P, Ronkko S, Pelkonenb J, Tammic M, Urtti A (2003) Extracellular and intracellular barriers in non-viral gene delivery. J Control Release 93:213–217

    Article  Google Scholar 

  • Schuber F, Kichler A, Boeckler C, Frisch B (1998) Liposomes: from membrane models to gene therapy. Pure Appl Chem 70:89–96

    Article  CAS  Google Scholar 

  • Thanou M, Florea BI, Geldof M, Junginger HE, Borchard G (2002) Quaternized chitosan oligomers as novel gene delivery vectors in epithelial cell lines. Biomaterials 23:153–159

    Article  CAS  Google Scholar 

  • Tripathy SK, Black HB, Goldwasser E, Leiden JM (1996) Immune responses to transgene-encoded proteins limit the stability of gene expression after injection of replication-defective adenovirus vectors. Nat Med 2:545–550

    Article  CAS  Google Scholar 

Download references

Acknowledgement

This work was supported by the Regional Research Centers Program of the Korean Ministry of Educational and Human Resources Development through the center for Healthcare Technology Development.

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Authors and Affiliations

  1. Department of Bionanosystem Engineering, Chonbuk National University, Chonju, 561-756, Republic of Korea

    Shanta Raj Bhattarai, Remant Bahadur K.C. & Santosh Aryal

  2. Department of Materials Science and Engineering, University of Washington, Seattle, WA, 98195, USA

    Narayan Bhattarai

  3. Department of Pediatrics, School of Medicine, Chonbuk National University, Chonju, 561-756, Republic of Korea

    Sun Young Kim & Pyoung Han Hwang

  4. Department of Biochemistry, School of Dentisty, Chonbuk National University, Chonju, 561-756, Republic of Korea

    Ho Keun Yi

  5. Department of Textile Engineering, Chonbuk National University, Chonju, 561-756, Republic of Korea

    Hak Yong Kim

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  1. Shanta Raj Bhattarai
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  2. Remant Bahadur K.C.
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  3. Santosh Aryal
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  4. Narayan Bhattarai
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  5. Sun Young Kim
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  6. Ho Keun Yi
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  7. Pyoung Han Hwang
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  8. Hak Yong Kim
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Correspondence to Hak Yong Kim.

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Bhattarai, S.R., K.C., R., Aryal, S. et al. Hydrophobically modified chitosan/gold nanoparticles for DNA delivery. J Nanopart Res 10, 151–162 (2008). https://doi.org/10.1007/s11051-007-9233-7

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  • DOI: https://doi.org/10.1007/s11051-007-9233-7

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