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Amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposites for enhanced gene delivery

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Abstract

In this work a novel strategy has been developed to prepare well-dispersed amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposite (NH2-SiO2@LDH) via electrostatic interactions and condensation of (3-aminopropyl)triethoxysilane (APTES). This nanocomposite system is well dispersed in culture media and phosphate buffered saline, and exhibits low cytotoxicity and good biocompatibility. The fluorescence microscopy images and flow cytometry data indicate that such an NH2-SiO2@LDH nanocomposite is able to efficiently deliver small interfering RNA (siRNA) into the U2OS cell line to inhibit cell proliferation. Thus, NH2-SiO2@LDH nanocomposite has a great potential as a nanocarrier for efficient gene delivery.

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References

  1. Tan, S. J.; Kiatwuthinon, P.; Roh, Y. H.; Kahn, J. S.; Luo, D. Engineering nanocarriers for siRNA delivery. Small 2011, 7, 841–856.

    Article  Google Scholar 

  2. Davis, M. E.; Zuckerman, J. E.; Choi, C. H. J.; Seligson, D.; Tolcher, A.; Alabi, C. A.; Yen, Y.; Heidel, J. D.; Ribas, A. Evidence of RNAi in humans from systemically administered siRNA via targeted nanoparticles. Nature 2010, 464, 1067–1070.

    Article  Google Scholar 

  3. Oh, Y. K.; Park, T. G. siRNA delivery systems for cancer treatment. Adv. Drug Delivery Rev. 2009, 61, 850–862.

    Article  Google Scholar 

  4. Elbashir, S. M.; Harborth, J.; Lendeckel, W.; Yalcin, A.; Weber, K.; Tuschl, T. Duplexes of 21-nucleotide RNAs mediate RNA interference in cultured mammalian cells. Nature 2001, 411, 494–498.

    Article  Google Scholar 

  5. Chen, M.; Cooper, H. M.; Zhou, J. Z.; Bartlett, P. F.; Xu, Z. P. Reduction in the size of layered double hydroxide nanoparticles enhances the efficiency of sirna delivery. J. Colloid Interface Sci. 2013, 390, 275–281.

    Article  Google Scholar 

  6. Tseng, Y. C.; Mozumdar, S.; Huang, L. Lipid-based systemic delivery of siRNA. Adv. Drug Delivery Rev. 2009, 61, 721–731.

    Article  Google Scholar 

  7. Li, J.; Wang, Y.; Zhu, Y.; Oupický, D. Recent advances in delivery of drug-nucleic acid combinations for cancer treatment. J. Controlled Release 2013, 172, 589–600.

    Article  Google Scholar 

  8. Tang, F.; Li, L.; Chen, D. Mesoporous silica nanoparticles: Synthesis, biocompatibility and drug delivery. Adv. Mater. 2012, 24, 1504–1534.

    Article  Google Scholar 

  9. Peer, D.; Karp, J. M.; Hong, S.; Farokhzad, O. C.; Margalit, R.; Langer, R. Nanocarriers as an emerging platform for cancer therapy. Nat. Nanotechnol. 2007, 2, 751–760.

    Article  Google Scholar 

  10. Ladewig, K.; Niebert, M.; Xu, Z. P.; Gray, P. P.; Lu, G. Q. M. Efficient siRNA delivery to mammalian cells using layered double hydroxide nanoparticles. Biomaterials 2010, 31, 1821–1829.

    Article  Google Scholar 

  11. Chang, R. S.; Suh, M. S.; Kim, S.; Shim, G.; Lee, S.; Han, S. S.; Lee, K. E.; Jeon, H.; Choi, H. G.; Choi, Y. et al. Cationic drug-derived nanoparticles for multifunctional delivery of anticancer sirna. Biomaterials 2011, 32, 9785–9795.

    Article  Google Scholar 

  12. Xu, Z. P.; Niebert, M.; Porazik, K.; Walker, T. L.; Cooper, H. M.; Middelberg, A. P. J.; Gray, P. P.; Bartlett, P. F.; Lu, G. Q. Subcellular compartment targeting of layered double hydroxide nanoparticles. J. Controlled Release 2008, 130, 86–94.

    Article  Google Scholar 

  13. Ladewig, K.; Xu, Z. P.; Lu, G. Q. Layered double hydroxide nanoparticles in gene and drug delivery. Expert Opin. Drug Delivery 2009, 6, 907–922.

    Article  Google Scholar 

  14. Khan, A. I.; Ragavan, A.; Fong, B.; Markland, C.; O’Brien, M.; Dunbar, T. G.; Williams, G. R.; O’Hare, D. Recent developments in the use of layered double hydroxides as host materials for the storage and triggered release of functional anions. Ind. Eng. Chem. Res. 2009, 48, 10196–10205.

    Article  Google Scholar 

  15. Choi, S. J.; Choy, J. H. Layered double hydroxide nanoparticles as target-specific delivery carriers: Uptake mechanism and toxicity. Nanomedicine 2011, 6, 803–814.

    Article  Google Scholar 

  16. Wong, Y.; Markham, K.; Xu, Z. P.; Chen, M.; Lu, G. Q.; Bartlett, P. F.; Cooper, H. M. Efficient delivery of siRNA to cortical neurons using layered double hydroxide nanoparticles. Biomaterials 2010, 31, 8770–8779.

    Article  Google Scholar 

  17. Wong, Y. Y.; Cooper, H. M.; Zhang, K.; Chen, M.; Bartlett, P.; Xu, Z. P. Efficiency of layered double hydroxide nanoparticle-mediated delivery of siRNA is determined by nucleotide sequence. J. Colloid Interface Sci. 2012, 369, 453–459.

    Article  Google Scholar 

  18. Choi, S. J.; Oh, J. M.; Choy, J. H. Anticancer drug-layered hydroxide nanohybrids as potent cancer chemotherapy agents. J. Phys. Chem. Solids 2008, 69, 1528–1532.

    Article  Google Scholar 

  19. Sakurai, Y.; Hatakeyama, H.; Sato, Y.; Akita, H.; Takayama, K.; Kobayashi, S.; Futaki, S.; Harashima, H. Endosomal escape and the knockdown efficiency of liposomal-siRNA by the fusogenic peptide shGALA. Biomaterials 2011, 32, 5733–5742.

    Article  Google Scholar 

  20. Taratula, O.; Kuzmov, A.; Shah, M.; Garbuzenko, O. B.; Minko, T. Nanostructured lipid carriers as multifunctional nanomedicine platform for pulmonary co-delivery of anticancer drugs and siRNA. J. Controlled Release 2013, 171, 349–357.

    Article  Google Scholar 

  21. Oh, J. M.; Choi, S. J.; Lee, G. E.; Han, S. H.; Choy, J. H. Inorganic drug-delivery nanovehicle conjugated with cancer-cell-specific ligand. Adv. Funct. Mater. 2009, 19, 1617–1624.

    Article  Google Scholar 

  22. Zhu, Y.; Li, Z.; Chen, M.; Cooper, H. M.; Lu, G. Q.; Xu, Z. P. Synthesis of robust sandwich-like SiO2@CdTe@SiO2 fluorescent nanoparticles for cellular imaging. Chem. Mater. 2012, 24, 421–423.

    Article  Google Scholar 

  23. Shao, M. F.; Ning, F. Y.; Zhao, J. W.; Wei, M.; Evans, D. G.; Duan, X. Preparation of Fe3O4@SiO2@layered double hydroxide core-shell microspheres for magnetic separation of proteins. J. Am. Chem. Soc. 2012, 134, 1071–1077.

    Article  Google Scholar 

  24. Du, X. J.; Zhang, D. S.; Gao, R. H.; Huang, L.; Shi, L. Y.; Zhang, J. P. Design of modular catalysts derived from NiMgAl-LDH@m-SiO2 with dual confinement effects for dry reforming of methane. Chem. Commun. 2013, 49, 6770–6772.

    Article  Google Scholar 

  25. Liu, J.; Harrison, R.; Zhou, J. Z.; Liu, T. T.; Yu, C.; Lu, G. Q.; Qiao, S. Z.; Xu, Z. P. Synthesis of nanorattles with layered double hydroxide core and mesoporous silica shell as delivery vehicles. J. Mater. Chem. 2011, 21, 10641–10644.

    Article  Google Scholar 

  26. Gary-Bobo, M.; Hocine, O.; Brevet, D.; Maynadier, M.; Raehm, L.; Richeter, S.; Charasson, V.; Loock, B.; Morère, A.; Maillard, P. et al. Cancer therapy improvement with mesoporous silica nanoparticles combining targeting, drug delivery and PDT. Int. J. Pharm. 2012, 423, 509–515.

    Article  Google Scholar 

  27. Roesch, A.; Vultur, A.; Bogeski, I.; Wang, H.; Zimmermann, K. M.; Speicher, D.; Körbel, C.; Laschke, M. W.; Gimotty, P. A.; Philipp, S. E. et al. Overcoming intrinsic multidrug resistance in melanoma by blocking the mitochondrial respiratory chain of slow-cycling JARID1Bhigh cells. Cancer Cell 2013, 23, 811–825.

    Article  Google Scholar 

  28. Rosenholm, J. M.; Sahlgren, C.; Linden, M. Towards multifunctional, targeted drug delivery systems using mesoporous silica nanoparticles-opportunities & challenges. Nanoscale 2010, 2, 1870–1883.

    Article  Google Scholar 

  29. Gu, W. Y.; Jia, Z. F.; Truong, N. P.; Prasadam, I.; Xiao, Y.; Monteiro, M. J. Polymer nanocarrier system for endosome escape and timed release of sirna with complete gene silencing and cell death in cancer cells. Biomacromolecules 2013, 14, 3386–3389.

    Article  Google Scholar 

  30. Xu, Z. P.; Stevenson, G.; Lu, C. Q.; Lu, G. Q.; Bartlett, P. F.; Gray, P. Stable suspension of layered double hydroxide nanoparticles in aqueous solution. J. Am. Chem. Soc. 2006, 128, 36–37.

    Article  Google Scholar 

  31. Yokoi, T.; Sakamoto, Y.; Terasaki, O.; Kubota, Y.; Okubo, T.; Tatsumi, T. Periodic arrangement of silica nanospheres assisted by amino acids. J. Am. Chem. Soc. 2006, 128, 13664–13665.

    Article  Google Scholar 

  32. Li, L.; Gu, W. Y.; Chen, J. Z.; Chen, W. Y.; Xu, Z. P. Co-delivery of siRNAs and anti-cancer drugs using layered double hydroxide nanoparticles. Biomaterials 2014, 35, 3331–3339.

    Article  Google Scholar 

  33. Hartlen, K. D.; Athanasopoulos, A. P. T.; Kitaev, V. Facile preparation of highly monodisperse small silica spheres (15 to >200 nm) suitable for colloidal templating and formation of ordered arrays. Langmuir 2008, 24, 1714–1720.

    Article  Google Scholar 

  34. Xu, Z. P.; Stevenson, G.; Lu, C. Q.; Lu, G. Q. Dispersion and size control of layered double hydroxide nanoparticles in aqueous solutions. J. Phys. Chem. 2006, 110, 16923–16929.

    Article  Google Scholar 

  35. Gu, Z.; Thomas, A. C.; Xu, Z. P.; Campbell, J. H.; Lu, G. Q. In vitro sustained release of LMWH from MgAl-layered double hydroxide nanohybrids. Chem. Mater. 2008, 20, 3715–3722.

    Article  Google Scholar 

  36. Mandel, K.; Drenkova-Tuhtan, A.; Hutter, F.; Gellermann, C.; Steinmetz, H.; Sextl, G. Layered double hydroxide ion exchangers on superparamagnetic microparticles for recovery of phosphate from waste water. J. Mater. Chem. 2013, 1, 1840–1848.

    Article  Google Scholar 

  37. Hartono, S. B.; Gu, W. Y.; Kleitz, F.; Liu, J.; He, L. Z.; Middelberg, A. P. J.; Yu, C. Z.; Lu, G. Q.; Qiao, S. Z. Poly-L-lysine functionalized large pore cubic mesostructured silica nanoparticles as biocompatible carriers for gene delivery. ACS Nano 2012, 6, 2104–2117.

    Article  Google Scholar 

  38. Yu, C.; Chu, H.; Wan, Y.; Zhao, D. Synthesis of easily shaped ordered mesoporous titanium-containing silica. J. Mater. Chem. 2010, 20, 4705–4714.

    Article  Google Scholar 

  39. Mishra, M.; Das, M.; Goswamee, R. Synthesis and coating of silica supported nickel oxide particles over ceramic pre-forms through sol-gel derived layered double hydroxides. J. Sol-Gel Sci. Technol. 2010, 54, 57–61.

    Article  Google Scholar 

  40. Choi, S. J.; Oh, J. M.; Park, T.; Choy, J. H. Cellular toxicity of inorganic hydroxide nanoparticles. J. Nanosci. Nanotechnol. 2007, 7, 4017–4020.

    Article  Google Scholar 

  41. Slowing, I. I.; Wu, C. W.; Vivero-Escoto, J. L.; Lin, V. S. Y. Mesoporous silica nanoparticles for reducing hemolytic activity towards mammalian red blood cells. Small 2009, 5, 57–62.

    Article  Google Scholar 

  42. Yu, T.; Malugin, A.; Ghandehari, H. Impact of silica nanoparticle design on cellular toxicity and hemolytic activity. ACS Nano 2011, 5, 5717–5728.

    Article  Google Scholar 

  43. Paula, A. J.; Martinez, D. S. T.; Araujo Júnior, R. T.; Souza Filho, A. G.; Alves, O. L. Suppression of the hemolytic effect of mesoporous silica nanoparticles after protein corona interaction: Independence of the surface microchemical environment. J. Braz. Chem. Soc. 2012, 23, 1807–1814.

    Article  Google Scholar 

  44. Gu, J.; Su, S.; Li, Y.; He, Q.; Shi, J. Hydrophilic mesoporous carbon nanoparticles as carriers for sustained release of hydrophobic anti-cancer drugs. Chem. Commun. 2011, 47, 2101–2103.

    Article  Google Scholar 

  45. Truong, N. P.; Gu, W.; Prasadam, I.; Jia, Z.; Crawford, R.; Xiao, Y.; Monteiro, M. J. An influenza virus-inspired polymer system for the timed release of sirna. Nat. Commun. 2013, 4, 1902.

    Article  Google Scholar 

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Correspondence to Zhi Ping Xu.

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Li, L., Gu, W., Liu, J. et al. Amine-functionalized SiO2 nanodot-coated layered double hydroxide nanocomposites for enhanced gene delivery. Nano Res. 8, 682–694 (2015). https://doi.org/10.1007/s12274-014-0552-6

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  • DOI: https://doi.org/10.1007/s12274-014-0552-6

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