Skip to main content
Log in

Novel amino-modified silica nanoparticles as efficient vector for hepatocellular carcinoma gene therapy

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

Due to the ineffective conventional treatment for hepatocellular carcinoma (HCC), the nonviral gene delivery system has been proved to be an attractive alternative to HCC therapy. In this work, we have developed a kind of new self-assembled nanoparticles, which were named as amino-modified silica nanoparticles (AMSNs). Scanning electron microscopy and zeta potential results demonstrated that AMSNs had a diameter of 20–30 nm and positive surface charges of +11.3 mV, respectively. The AMSNs could bind DNA strongly and protect DNA from degradation, which was confirmed by DNA-binding assay and serum protection assay. Furthermore, AMSNs could transfer foreign DNA into targeted cells with high transfection efficiency and little cytotoxicity. Combined with the p53 gene, AMSNs could transfect pp53-EGFP in HepG2 cells and result in a high-level of p53 mRNA and protein expressions. The nude mice treated with AMSNs/pp53-EGFP complexes showed significant tumor growth inhibition. Our results showed the AMSNs, an efficient gene vector, had the potential of gene therapy for HCC.

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7
Fig. 8
Fig. 9
Fig. 10
Fig. 11

Similar content being viewed by others

References

  1. Müller C. Hepatocellular carcinoma-rising incidence, changing therapeutic strategies. Wien Med Wochenschr. 2006;156:404–9.

    Article  PubMed  Google Scholar 

  2. Jen CP, et al. A nonviral transfection approach in vitro: the design of a gold nanoparticle vector joint with microelectromechanical systems. Langmuir. 2004;20:1369–74.

    Article  CAS  PubMed  Google Scholar 

  3. Welzel T, Radtke I, Meyer-Zaika W, Heumann R, Epple M. Transfection of cells with custom-made calcium phosphate nanoparticles coated with DNA. J Mater Chem. 2004;14:2213–7.

    Article  CAS  Google Scholar 

  4. Chung TH, et al. The effect of surface charge on the uptake and biological function of mesoporous silica nanoparticles in 3T3-L1 cells and human mesenchymal stem cells. Biomaterials. 2007;28:2959–66.

    Article  CAS  PubMed  Google Scholar 

  5. Yan SF, et al. Surface-grafted silica linked with l-lactic acid oligomer: a novel nanofiller to improve the performance of biodegradable poly (l-lactide). Polymer. 2007;48:1688–94.

    Article  CAS  Google Scholar 

  6. Kim MI, et al. Immobilization of Mucor javanicus lipase on effectively functionalized silica nanoparticles. J Mol Catal B: Enzym. 2006;39:62–8.

    Article  CAS  Google Scholar 

  7. Park ME, Chang JH. High throughput human DNA purification with aminosilanes tailored silica-coated magnetic nanoparticles. Mat Sci Eng: C. 2007;27:1232–5.

    Article  CAS  Google Scholar 

  8. Chiang CL, Sung CS, Chen CY. Application of silica-magnetite nanocomposites to the isolation of ultrapure plasmid DNA from bacterial cells. J Magn Magn Mater. 2006;305:483–90.

    Article  CAS  Google Scholar 

  9. He XX, et al. Plasmid DNA isolation using amino-silica coated magnetic nanoparticles (ASMNPs). Talanta. 2007;73:764–9.

    Article  CAS  PubMed  Google Scholar 

  10. Yang W, Zhang CG, Qu HY, Yang HH, Xu JG. Novel fluorescent silica nanoparticle probe for ultrasensitive immunoassays. Anal Chim Acta. 2004;503:163–9.

    Article  CAS  Google Scholar 

  11. Wang XY, et al. Detection of thrombin using electrogenerated chemiluminescence based on Ru(bpy) 2+3 -doped silica nanoparticle aptasensor via target protein-induced strand displacement. Anal Chim Acta. 2007;598:242–8.

    Article  CAS  PubMed  Google Scholar 

  12. Kneuer C, et al. Silica nanoparticles modified with aminosilanes as carriers for plasmid DNA. Int J Pharm. 2000;196:257–61.

    Article  CAS  PubMed  Google Scholar 

  13. Hussain SP, Schwank J, Staib F, Wang XW, Harris CC. TP53 mutations and hepatocellular carcinoma: insights into the etiology and pathogenesis of liver cancer. Oncogene. 2007;26:2166–76.

    Article  CAS  PubMed  Google Scholar 

  14. Staib F, Hussain SP, Hofseth LJ. TP53 and liver carcinogenesis. Hum Mutat. 2003;21:2012–6.

    Article  CAS  Google Scholar 

  15. Guan YS, La Z, Yang L, He Q, Li P. p53 gene in treatment of hepatic carcinoma: status quo. World J Gastroenterol. 2007;13:985–92.

    CAS  PubMed  Google Scholar 

  16. Haupt S, Haupt Y. Importance of p53 for cancer onset and therapy. Anticancer Drug. 2006;17:725–32.

    Article  CAS  Google Scholar 

  17. Plumeré N, Speiser B. Redox-active silica nanoparticles: part 2. Photochemical hydrosilylation on a hydride modified silica particle surface for the covalent immobilization of ferrocene. Electrochim Acta. 2007;53:1245–52.

    Article  CAS  Google Scholar 

  18. Major RC, Zhu XY. Two-step approach to the formation of organic monolayers on the silicon oxide surface. Langmuir. 2001;17:5576–80.

    Article  CAS  Google Scholar 

  19. Varbiro G, Veres B, Gallyas F Jr, Sumegi B. Direct effect of taxol on free radical formation and mitochondrial permeability transition. Free Radic Biol Med. 2001;31:548–58.

    Article  CAS  PubMed  Google Scholar 

  20. He QQ, et al. Cell transformation and proteome alteration in QSG7701 cells transfected with hepatitis C virus non-structural protein 3. Acta Biochim Biophys Sin. 2007;39:751–62.

    Article  CAS  PubMed  Google Scholar 

  21. Sadasivan S, Rasmussen DH, Chen FP, Kannabiran RK. Preparation and characterization of ultrafine silica. Colloid Surface A. 1998;132:45–52.

    Article  CAS  Google Scholar 

  22. Chen Y, et al. Sodium chloride modified silica nanoparticles as a non-viral vector with a high efficiency of DNA transfer into cells. Curr Gene Ther. 2003;3:273–9.

    Article  CAS  PubMed  Google Scholar 

  23. He XX, et al. A novel DNA-enrichment technology based on aminomodified functionalised silica nanoparticles. J Disper Sci Technol. 2003;24:633–40.

    Article  CAS  Google Scholar 

  24. Zhu SG, et al. Poly(l-lysine)-modified silica nanoparticles for the delivery of antisense oligonucleotides. Biotechnol Appl Bioc. 2004;39:179–87.

    Article  CAS  Google Scholar 

  25. Bianco A, Kostarelos K, Partidos CD, Prato M. Biomedical applications of functionalized carbon nanotubes. Chem Commun. 2005;5:571–7.

    Article  CAS  Google Scholar 

  26. El Far MA, Atwa MA, Yahya RS, El Basuni MA. Evaluation of serum levels of p53 in hepatocellular carcinoma in Egypt. Clin Chem Lab Med. 2006;44:653–6.

    Article  CAS  PubMed  Google Scholar 

  27. Horowitz J. Adenovirus-mediated p53 gene therapy: overview of preclinical studies and potential clinical applications. Curr Opin Mol Ther. 1999;1:500–9.

    CAS  PubMed  Google Scholar 

  28. Guo Y, et al. Therapeutic potential of recombinant adenovirus expressing p53 in hepatocellular carcinoma cell lines. Zhonghua Ganzangbing Zazhi. 2001;9:S43–5.

    Google Scholar 

  29. Wang W, Rastinejad F, El-Deiry WS. Restoring p53-dependent tumor suppression. Cancer Biol Ther. 2003;2:S55–63.

    CAS  PubMed  Google Scholar 

  30. Nowling T, Desler M, Kuszynski C, Rizzino A. Transfection of embryonal carcinoma cells at efficiency using liposome-mediated transfection. Mol Reprod Dev. 2002;63:309–17.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (grant no. 20376085) and the Hunan National Science Foundation (grant no. 09JJ5030).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kelong Huang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Xiao, X., He, Q. & Huang, K. Novel amino-modified silica nanoparticles as efficient vector for hepatocellular carcinoma gene therapy. Med Oncol 27, 1200–1207 (2010). https://doi.org/10.1007/s12032-009-9359-9

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12032-009-9359-9

Keywords

Navigation