ABSTRACT
Purpose
Cationic lipid-coated gold nanoparticles were developed for efficient intracellular delivery of therapeutic siRNA.
Methods
Particle formation was characterized by UV-visible spectroscopy, atomic force microscopy, and dynamic light scattering analysis. Cellular uptake, gene silencing effect, and cytotoxicity were investigated in multiple human cancer cell lines.
Results
Nanoparticles had a spherical nanostructure with highly cationic surface charge and could form stable nanosized polyelectrolyte complexes with siRNA via electrostatic interactions; complexes exhibited efficient intracellular uptake and significant gene silencing effect with markedly low cytotoxicity compared to the widely used polycationic carrier, linear polyethyleneimine.
Conclusions
We demonstrated that cationic lipid-coated gold nanoparticles could be widely utilized as efficient and safe siRNA nanocarriers for diverse therapeutic and diagnostic applications.
Similar content being viewed by others
REFERENCES
Ghosh P, Han G, De M, Kim CK, Rotello VM. Gold nanoparticles in delivery applications. Adv Drug Deliv Rev. 2008;60:1307–15.
Guo S, Huang Y, Jiang Q, Sun Y, Deng L, Liang Z, et al. Enhanced gene delivery and siRNA silencing by gold nanoparticles coated with charge-reversal polyelectrolyte. ACS Nano. 2010;4:5505–11.
Lee JS, Green JJ, Love KT, Sunshine J, Langer R, Anderson DG. Gold, poly(beta-amino ester) nanoparticles for small interfering RNA delivery. Nano Lett. 2009;9:2402–6.
Giljohann DA, Seferos DS, Prigodich AE, Patel PC, Mirkin CA. Gene regulation with polyvalent siRNA-nanoparticle conjugates. J Am Chem Soc. 2009;131:2072–3.
Elbakry A, Zaky A, Liebl R, Rachel R, Goepferich A, Breunig M. Layer-by-layer assembled gold nanoparticles for siRNA delivery. Nano Lett. 2009;9:2059–64.
Rhim WK, Kim JS, Nam JM. Lipid-gold-nanoparticle hybrid-based gene delivery. Small. 2008;4:1651–5.
Li P, Li D, Zhang L, Li G, Wang E. Cationic lipid bilayer coated gold nanoparticles-mediated transfection of mammalian cells. Biomaterials. 2008;29:3617–24.
Y. Lee, S.H. Lee, J.S. Kim, A. Maruyama, X. Chen, and T.G. Park. Controlled synthesis of PEI-coated gold nanoparticles using reductive catechol chemistry for siRNA delivery. J Control Release (2010).
T. Niidome, K. Nakashima, H. Takahashi, and Y. Niidome. Preparation of primary amine-modified gold nanoparticles and their transfection ability into cultivated cells. Chem Commun (Camb):1978-1979 (2004).
Rosi NL, Giljohann DA, Thaxton CS, Lytton-Jean AK, Han MS, Mirkin CA. Oligonucleotide-modified gold nanoparticles for intracellular gene regulation. Science. 2006;312:1027–30.
Kubowicz S, Daillant J, Dubois M, Delsanti M, Verbavatz JM, Mohwald H. Mixed-monolayer-protected gold nanoparticles for emulsion stabilization. Langmuir. 2010;26:1642–8.
Cormode DP, Skajaa T, van Schooneveld MM, Koole R, Jarzyna P, Lobatto ME, et al. Nanocrystal core high-density lipoproteins: a multimodality contrast agent platform. Nano Lett. 2008;8:3715–23.
Mok H, Lee SH, Park JW, Park TG. Multimeric small interfering ribonucleic acid for highly efficient sequence-specific gene silencing. Nat Mater. 2010;9:272–8.
Higuchi Y, Kawakami S, Hashida M. Strategies for in vivo delivery of siRNAs: recent progress. BioDrugs. 2010;24:195–205.
Gilmore IR, Fox SP, Hollins AJ, Akhtar S. Delivery strategies for siRNA-mediated gene silencing. Curr Drug Deliv. 2006;3:147–5.
Park TG, Jeong JH, Kim SW. Current status of polymeric gene delivery systems. Adv Drug Deliv Rev. 2006;58:467–86.
Mokand H, Park TG. Functional polymers for targeted delivery of nucleic acid drugs. Macromol Biosci. 2009;9:731–43.
Ohand YK, Park TG. siRNA delivery systems for cancer treatment. Adv Drug Deliv Rev. 2009;61:850–62.
Mevel M, Kamaly N, Carmona S, Oliver MH, Jorgensen MR, Crowther C, et al. DODAG; a versatile new cationic lipid that mediates efficient delivery of pDNA and siRNA. J Control Release. 2010;143:222–32.
Semple SC, Akinc A, Chen J, Sandhu AP, Mui BL, Cho CK, et al. Rational design of cationic lipids for siRNA delivery. Nat Biotechnol. 2010;28:172–6.
Schroeder A, Levins CG, Cortez C, Langer R, Anderson DG. Lipid-based nanotherapeutics for siRNA delivery. J Intern Med. 2010;267:9–21.
Mukherjee S, Ray S, Thakur RS. Solid lipid nanoparticles: a modern formulation approach in drug delivery system. Indian J Pharm Sci. 2009;71:349–58.
Kim HR, Kim IK, Bae KH, Lee SH, Lee Y, Park TG. Cationic solid lipid nanoparticles reconstituted from low density lipoprotein components for delivery of siRNA. Mol Pharm. 2008;5:622–31.
Akinc A, Querbes W, De S, Qin J, Frank-Kamenetsky M, Jayaprakash KN, et al. Targeted delivery of RNAi therapeutics with endogenous and exogenous ligand-based mechanisms. Mol Ther. 2010;18:1357–64.
Kim SI, Shin D, Lee H, Ahn BY, Yoon Y, Kim M. Targeted delivery of siRNA against hepatitis C virus by apolipoprotein A-I-bound cationic liposomes. J Hepatol. 2009;50:479–88.
Tao W, Davide JP, Cai M, Zhang GJ, South VJ, Matter A, et al. Noninvasive imaging of lipid nanoparticle-mediated systemic delivery of small-interfering RNA to the liver. Mol Ther. 2010;18:1657–66.
Zheng N, Fan J, Stucky GD. One-step one-phase synthesis of monodisperse noble-metallic nanoparticles and their colloidal crystals. J Am Chem Soc. 2006;128:6550–1.
Brust M. Nanoparticle ensembles: nanocrystals come to order. Nat Mater. 2005;4:364–5.
Couto RD, Dallan LA, Lisboa LA, Mesquita CH, Vinagre CG, Maranhao RC. Deposition of free cholesterol in the blood vessels of patients with coronary artery disease: a possible novel mechanism for atherogenesis. Lipids. 2007;42:411–8.
Lauer ME, Grassmann O, Siam M, Tardio J, Jacob L, Page S, et al. Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions. Pharm Res. 2011;28:572–84.
Ueda Y, Yamagishi T, Samata K, Ikeya H, Hirayama N, Takashima H, et al. A novel low molecular weight antagonist of vascular endothelial growth factor receptor binding: VGA1155. Mol Cancer Ther. 2003;2:1105–11.
Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. Local and systemic delivery of VEGF siRNA using polyelectrolyte complex micelles for effective treatment of cancer. Journal of controlled release: official journal of the Controlled Release Society. 2008;129:107–16.
Kim SH, Jeong JH, Lee SH, Kim SW, Park TG. PEG conjugated VEGF siRNA for anti-angiogenic gene therapy. Journal of controlled release: official journal of the Controlled Release Society. 2006;116:123–9.
Wu P, Tian Y, Chen G, Wang B, Gui L, Xi L, et al. Ubiquitin B: an essential mediator of trichostatin A-induced tumor-selective killing in human cancer cells. Cell Death Differ. 2010;17:109–18.
Chenand D, Dou QP. The ubiquitin-proteasome system as a prospective molecular target for cancer treatment and prevention. Curr Protein Pept Sci. 2010;11:459–70.
M.F. Yuenand C.L. Lai. Treatment of chronic hepatitis B: Evolution over two decades. J Gastroenterol Hepatol. 26 Suppl 1:138-143 (2011).
Fu J, Tang ZM, Gao X, Zhao F, Zhong H, Wen MR, et al. Optimal design and validation of antiviral siRNA for targeting hepatitis B virus. Acta Pharmacol Sin. 2008;29:1522–8.
Chen Y, Cheng G, Mahato RI. RNAi for treating hepatitis B viral infection. Pharm Res. 2008;25:72–86.
Hainfeld JF, Slatkin DN, Focella TM, Smilowitz HM. Gold nanoparticles: a new X-ray contrast agent. Br J Radiol. 2006;79:248–53.
ACKNOWLEDGMENTS & DISCLOSURES
The late Professor Tae Gwan Park supervised the overall work as a principal investigator. All coauthors deeply appreciate his invaluable contribution and educational efforts. This research was supported by the Ministry for Health, Welfare and Family Affairs, and the World Class University project, Basic Science Research Program (2010–0027955) from the Ministry of Education, Science and Technology, Republic of Korea.
Author information
Authors and Affiliations
Corresponding author
Additional information
Won Ho Kong and Ki Hyun Bae contributed equally to this work as first authors. The authors express their sincere condolences to family on the death (April 10, 2011) of Prof. Tae Gwan Park.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Supplemental Figure 1
(PDF 111 kb)
Supplemental Figure 2
(PDF 82.3 kb)
Supplemental Figure 3
(PDF 113 kb)
Supplemental Figure 4
(PDF 120 kb)
Rights and permissions
About this article
Cite this article
Kong, W.H., Bae, K.H., Jo, S.D. et al. Cationic Lipid-Coated Gold Nanoparticles as Efficient and Non-Cytotoxic Intracellular siRNA Delivery Vehicles. Pharm Res 29, 362–374 (2012). https://doi.org/10.1007/s11095-011-0554-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11095-011-0554-y