Skip to main content
Log in

Self-assemblies of plasmonic gold/layered double hydroxides with highly efficient antiviral effect against the hepatitis B virus

  • Research Article
  • Published:
Nano Research Aims and scope Submit manuscript

Abstract

Engineering complex nanocomposites that specifically target the hepatitis B virus (HBV) and overcome the limitations of current therapies such as limited efficacy and serious side effects is very challenging. Here, for the first time, the antiviral effect of engineered plasmonic gold and layered double hydroxide self-assemblies (AuNPs/LDHs) is demonstrated, using HBV as a model virus and hepatoma-derived HepG2.2.215 cells for viral replication, assembly, and secretion of infectious virions and subviral particles. AuNPs/LDHs were obtained by a simple, cost-effective procedure in which small AuNPs (~3.5 nm) were directly obtained and organized on the surface of larger LDH nanoparticles (~150 nm) by exploiting the capability of MgLDH, ZnLDH, and MgFeLDH to manifest their “structural memory” in the aqueous solution of Au(O2CCH3)3. The self-assembly approach of AuNPs and LDHs was assessed by transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS), powder X-ray diffraction (PXRD), and UV—Vis analysis (UV–Vis). All AuNPs/LDHs tested reduced the amount of viral and subviral particles released from treated cells by up to 80% and exhibited good cytocompatibility. AuNPs/MgFeLDH showed the highest antiviral HBV response with more than 90% inhibition of HBV secretion for the whole concentration range. Preliminary studies on the mechanism of HBV inhibition reveals that in the presence of AuNPs/LDHs, HBV particles are sequestered within the treated cells. The antiviral and low cytotoxic plasmonic properties of these Au/LDH nanocomposites indicate that they hold significant potential to be tailored as novel efficient therapeutics for the treatment of hepatitis B.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Parkin, D. M. Global cancer statistics in the year 2000. Lancet Oncol. 2001, 2, 533–543.

    Article  Google Scholar 

  2. Huang, T. J.; Chuang, H.; Liang, Y. C.; Lin, H. H.; Horng, J. C.; Kuo, Y. C; Chen, C. W.; Tsai, F. Y.; Yen, S. C.; Chou, S. C. et al. Design, synthesis, and bioevaluation of paeonol derivatives as potential anti-HBV agents. Eur. J. Med. Chem. 2015, 2, 428–435.

    Article  Google Scholar 

  3. Yu, W. Q.; Goddard, C.; Clearfield, E.; Mills, C.; Xiao, T.; Guo, H. T.; Morrey, J. D.; Motter, N. E.; Zhao, K.; Block, T. M. et al. Design, synthesis, and biological evaluation of triazolo-pyrimidine derivatives as novel inhibitors of hepatitis B virus surface antigen (HBsAg) secretion. J. Med. Chem. 2011, 2, 5660–5670.

    Article  Google Scholar 

  4. Block, T. M.; Gish, R.; Guo, H. T.; Mehta, A.; Cuconati, A.; Thomas London, W.; Guo, J. T. Chronic hepatitis B: What should be the goal for new therapies? Antiviral Res. 2013, 2, 27–34.

    Article  Google Scholar 

  5. Austin, L. A.; Mackey, M. A.; Dreaden, E. C.; El-Sayed, M. A. The optical, photothermal, and facile surface chemical properties of gold and silver nanoparticles in biodiagnostics, therapy, and drug delivery. Arch. Toxicol. 2014, 2, 1391–1417.

    Article  Google Scholar 

  6. Huang, T. J.; Chou, B. H.; Lin, C. W.; Weng, J. H.; Chou, C. H.; Yang, L. M.; Lin, S. J. Synthesis and antiviral effects of isosteviol-derived analogues against the hepatitis B virus. Phytochemistry 2014, 2, 107–114.

    Article  Google Scholar 

  7. Blecher, K.; Nasir, A.; Friedman, A. The growing role of nanotechnology in combating infectious disease. Virulence 2011, 2, 395–401.

    Article  Google Scholar 

  8. Yang, F.; Jin, C.; Subedi, S.; Lee, C. L.; Wang, Q.; Jiang, Y. J.; Li, J.; Di, Y.; Fu, D. L. Emerging inorganic nanomaterials for pancreatic cancer diagnosis and treatment. Cancer Treat. Rev. 2012, 2, 566–579.

    Article  Google Scholar 

  9. Dreaden, E. C.; El-Sayed, M. A. Detecting and destroying cancer cells in more than one way with noble metals and different confinement properties on the nanoscale. Acc. Chem. Res. 2012, 2, 1854–1865.

    Article  Google Scholar 

  10. Kennedy, L. C.; Bickford, L. R.; Lewinski, N. A.; Coughlin, A. J.; Hu, Y.; Day, E. S.; West, J. L.; Drezek, R. A. A new era for cancer treatment: Gold-nanoparticle-mediated thermal therapies. Small 2011, 2, 169–183.

    Article  Google Scholar 

  11. Luo, Y. L.; Shiao, Y. S.; Huang, Y. F. Release of photoactivatable drugs from plasmonic nanoparticles for targeted cancer therapy. ASC Nano 2011, 2, 7796–7804.

    Article  Google Scholar 

  12. Lewinski, N.; Colvin, V.; Drezek, R. Cytotoxicity of nanoparticles. Small 2008, 2, 26–49.

    Article  Google Scholar 

  13. Kostarelos, K.; Lacerda, L.; Pastorin, G.; Wu, W.; Kieckowski, S.; Luangsivilay, J.; Godefroy, S.; Pantarotto, D.; Briand, J. P.; Muller, S. et al. Cellular uptake of functionalized carbon nanotubes is independent of functional group and cell type. Nat. Nanotechnol. 2007, 2, 108–113.

    Article  Google Scholar 

  14. Thomas, M.; Klibanov, A. M. Conjugation to gold nanoparticles enhances polyethylenimine’s transfer of plasmid DNA into mammalian cells. Proc. Natl. Acad. Sci. USA. 2003, 2, 9138–9143.

    Article  Google Scholar 

  15. Mackey, M. A.; Ali, M. R. K.; Austin, L. A.; Near, R. D.; El-Sayed, M. A. The most effective gold nanorod size for plasmonic photothermal therapy: Theory and in vitro experiments. J. Phys. Chem. B 2014, 2, 1319–1326.

    Article  Google Scholar 

  16. Mahmoud, M. A.; El-Sayed, M. A. Different plasmon sensing behavior of silver and gold nanorods. J. Phys. Chem. Lett. 2013, 2, 1541–1545.

    Article  Google Scholar 

  17. Liu, J. B.; Yu, M. X.; Zhou, C.; Zheng, J. Renal clearable inorganic nanoparticles: A new frontier of bionanotechnology. Mater. Today 2013, 2, 477–486.

    Article  Google Scholar 

  18. Goh, D.; Gong, T. X.; Dinish, U. S.; Maiti, K. K.; Fu, C. Y.; Yong, K. T.; Olivo, M. Pluronic triblock copolymer encapsulated gold nanorods as biocompatible localized plasmon resonance-enhanced scattering probes for dark-field imaging of cancer cells. Plasmonics 2012, 2, 595–601.

    Article  Google Scholar 

  19. Zhang, X. D.; Wu, H. Y.; Wu, D.; Wang, Y. Y.; Chang, J. H.; Zhai, Z. B.; Meng, A. M.; Liu, P. X.; Zhang, L. A.; Fan, F. Y. Toxicologic effects of gold nanoparticles in vivo by different administration routes. Int. J. Nanomedicine. 2010, 2, 771–781.

    Article  Google Scholar 

  20. Dahl, J. A.; Maddux, B. L. S.; Hutchison, J. E. Toward greener nanosynthesis. Chem. Rev. 2007, 2, 2228–2269.

    Article  Google Scholar 

  21. Hou, W.; Cronin, S. B. A review of surface plasmon resonance-enhanced photocatalysis. Adv. Funct. Mater. 2013, 2, 1612–1619.

    Article  Google Scholar 

  22. Kawamura, S.; Puscasu, M. C.; Yoshida, Y.; Izumi, Y.; Carja, G. Tailoring assemblies of plasmonic silver/gold and zinc–gallium layered double hydroxides for photocatalytic conversion of carbon dioxide using UV–visible light. Appl. Catal. A: Gen., in press, DOI: 10.1016/j.apcata.2014.12.042.

  23. Carja, G.; Birsanu, M.; Okada, K.; Garcia, H. Composite plasmonic gold/layered double hydroxides and derived mixed oxides as novel photocatalysts for hydrogen generation under solar irradiation. J. Mater. Chem. A 2013, 2, 9092–9098.

    Article  Google Scholar 

  24. Seftel, E. M.; Puscasu, M. C.; Mertens, M.; Cool, P.; Carja, G. Fabrication of CeO2/LDHs self-assemblies with enhanced photocatalytic performance: A case study on ZnSn-LDH matrix. Appl. Catal. B: Environ. 2015, 2, 251–260.

    Article  Google Scholar 

  25. Valente, J. S.; Lima, E.; Toledo-Antonio, J. A.; Cortes- Jacome, M. A.; Lartundo-Rojas, L.; Montiel, R.; Prince, J. Comprehending the thermal decomposition and reconstruction process of sol-gel MgAl layered double hydroxides. J. Phys. Chem. C 2010, 2, 2089–2099.

    Article  Google Scholar 

  26. Prince, J.; Tzompantzi, F.; Mendoza-Damiá n, G.; Hernández- Beltrá nc, F.; Valente, J. S. Photocatalytic degradation of phenol by semiconducting mixed oxides derived from Zn(Ga)Al layered double hydroxides. Appl. Catal. B: Environ. 2015, 2, 352–360.

    Article  Google Scholar 

  27. Carja, G.; Dartu, L.; Okada, K.; Fortunato, E. Nanoparticles of copper oxide on layered double hydroxides and the derived solid solutions as wide spectrum active nano-photocatalysts. Chem. Eng. J. 2013, 2, 60–66.

    Article  Google Scholar 

  28. Ariga, K.; Ji, Q. M.; McShane, M. J.; Lvov, Y. M.; Vinu, A.; Hill, J. P. Inorganic nanoarchitectonics for biological applications. Chem. Mater. 2012, 2, 728–737.

    Article  Google Scholar 

  29. 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, 2, 1821–1829.

    Article  Google Scholar 

  30. Oh, J. M.; Choi, S. J.; Lee, G. E.; Kim, J. E.; Choy, J. H. Inorganic metal hydroxide nanoparticles for targeted cellular uptake through clathrin-mediated endocytosis. Chem. Asian J. 2009, 2, 67–73.

    Article  Google Scholar 

  31. Reichle, W. T.; Kang, S. Y.; Everhardt, D. S. The nature of the thermal decomposition of a catalytically active anionic clay mineral. J. Catal. 1986, 2, 352–359.

    Article  Google Scholar 

  32. Lazar, C.; Durantel, D.; Macovei, A.; Zitzmann, N.; Zoulim, F.; Dwek, R. A.; Branza-Nichita, N. Treatment of hepatitis B virus-infected cells with a-glucosidase inhibitors results in production of virions with altered molecular composition and infectivity. Antiviral Res. 2007, 2, 30–37.

    Article  Google Scholar 

  33. Rives, V.; del Arco, M.; Martin, C. Intercalation of drugs in layered double hydroxides and their controlled release: A review. Appl. Clay Sci. 2014, 88–89, 239–269.

    Article  Google Scholar 

  34. Rives, V. Layered Double Hydroxides: Present and Future; Nova Science Publishers: New York, 2011.

    Google Scholar 

  35. Louis, C.; Pluchery, O. Gold Nanoparticles for Physics, Chemistry, Biology; Imperial College Press: London, 2012.

    Book  Google Scholar 

  36. He, J. H.; Kunitake, T. Preparation and thermal stability of gold nanoparticles in silk-templated porous filaments of titania and zirconia. Chem. Mater. 2004, 2, 2656–2661.

    Article  Google Scholar 

  37. Alanis, C.; Natividad, R.; Barrera-Diaz, C.; Martí nez-Miranda, V.; Prince, J.; Valente, J. S. Photocatalytically enhanced Cr(VI) removal by mixed oxides derived from MeAl (Me: Mg and/ or Zn) layered double hydroxides. Appl. Catal. B: Environ. 2013, 140–141, 546–551.

    Article  Google Scholar 

  38. Hall, B. D.; Zanchet, D.; Ugarte, D. Estimating nanoparticle size from diffraction measurements. J. Appl. Cryst. 2000, 2, 1335–1341.

    Article  Google Scholar 

  39. Prevot, V.; Briois, V.; Cellier, J.; Forano C.; Leroux, F. An in-situ investigation of LDH–acetate prepared in polyol, under moderate thermal treatment. J. Phys. Chem. Solids 2008, 2, 1091–1094.

    Article  Google Scholar 

  40. Horváth, A.; Beck, A.; Stefler, G.; Benkó, T.; Sáfrán, G.; Varga, Z.; Gubicza, J.; Guczi, L. Silica-supported Au nanoparticles decorated by CeO2: Formation, morphology, and COoxidation activity. J. Phys. Chem. C 2011, 2, 20388–20398.

    Article  Google Scholar 

  41. Kominami, H.; Tanaka, A; Hashimoto, K. Gold nanoparticles supported on cerium(IV) oxide powder for mineralization of organic acids in aqueous suspensions under irradiation of visible light of λ = 530 nm. Appl. Catal. A: Gen. 2011, 2, 121–126.

    Article  Google Scholar 

  42. Corti, C.; Holliday, R. Gold: Science and Applications; CRC Press: UK, 2009.

    Book  Google Scholar 

  43. Zhou, C.; Yu, J.; Qin, Y. P.; Zheng, J. Grain size effects in polycrystalline gold nanoparticles. Nanoscale 2012, 2, 4228–4233.

    Article  Google Scholar 

  44. Mignani, A.; Ballarin, B.; Giorgetti, M.; Scavetta, E.; Tonelli, D.; Boanini, E.; Prevot, V.; Mousty, C.; Iadecola, A. Heterostructure of Au nanoparticles-NiAl layered double hydroxide: Electrosynthesis, characterization, and electrocatalytic properties. J. Phys Chem. C 2013, 2, 16221–16230.

    Article  Google Scholar 

  45. Patient, R.; Hourioux, C.; Roingeard, P. Morphogenesis of hepatitis B virus and its subviral envelope particles. Cell. Microbiol. 2009, 2, 1561–1570.

    Article  Google Scholar 

  46. Lu, L.; Sun, R. W.; Chen, R.; Hui, C. K.; Ho, C. M.; Luk, J. M.; Lau G. K. K.; Che, C. M. Silver nanoparticles inhibit hepatitis B virus replication. Antivir. Ther. 2008, 2, 253–262.

    Google Scholar 

  47. Bruss, V. Hepatitis B virus morphogenesis. World J. Gastroenterol. 2007, 2, 65–73.

    Article  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Gabriela Carja.

Electronic supplementary material

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Carja, G., Grosu, E.F., Petrarean, C. et al. Self-assemblies of plasmonic gold/layered double hydroxides with highly efficient antiviral effect against the hepatitis B virus. Nano Res. 8, 3512–3523 (2015). https://doi.org/10.1007/s12274-015-0851-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12274-015-0851-6

Keywords

Navigation