Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen

Gene Therapy volume 14, pages 828–835 (2007)Cite this article

Abstract

We have compared the ability of several nanosized bioceramic particles including negatively charged silica (SiO2), neutrally charged hydroxyapatite (HA) and positively charged zirconia (ZrO2) nanoparticles as non-viral vectors for efficient in vivo gene delivery. A mixture of highly monodispersed aqueous suspension of HA or SiO2 nanoparticles, coated with protamine sulfate (PS), complexed efficiently with plasmid DNA and significantly enhanced transgene expression in vitro. In comparison, ZrO2 nanoparticles gave poor transfection efficiency under similar conditions tested. It was also determined that, under the same conditions, PS-SiO2-DNA, but not PS-HA-DNA-nanoplexes, were able to mediate efficient transgene expression in vitro in the presence of 50% serum. Intraperitoneal injections of PS-SiO2-luciferase DNA nanoplexes targeted the highest level of transgene expression in the spleen of recipient mice that lasted for more than 48 h. Injection of PS-SiO2-pNGVL-hFLex-MUC-1 nanoplexes was able to mediate the production of Flt-3L in the sera of recipient mice. Simultaneously, the production of Flt-3L was accompanied by the stimulation of IL-2 and interferon-γ (IFN-γ). Most importantly, the injection of PS-SiO2-pNGVL-hFLex-MUC-1 nanoplexes could mount potent anti-tumour specific immune responses that led to the subsequent regression of parental tumor cells containing the muc-1 determinant.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4

Similar content being viewed by others

References

  1. Wagner E, Kircheis R, Walker GF . Targeted nucleic acid delivery into tumors: new avenues for cancer therapy. Biomed Pharmacother 2004; 58: 152–161.

    Article  CAS  Google Scholar 

  2. Wang Y, Yuan F . Delivery of viral vectors to tumor cells: extracellular transport, systemic distribution, and strategies for improvement Ann. Biomed Eng 2006; 34: 114–127.

    CAS  Google Scholar 

  3. Niidome T, Huang L . Gene therapy progress and prospects: nonviral vectors. Gene Ther 2002; 9: 1647–1652.

    Article  CAS  Google Scholar 

  4. Lawson C . Strategies for gene transfer to solid organs: viral vectors. Methods Mol Biol 2006; 333: 175–200.

    CAS  PubMed  Google Scholar 

  5. Glover DJ, Lipps HJ, Jans DA . Towards safe, non-viral therapeutic gene expression in humans. Nat Rev Genet 2005; 6: 299–310.

    Article  CAS  Google Scholar 

  6. Larin SS, Georgiev GP, Kiselev SL . Gene transfer approaches in cancer immunotherapy. Gene Ther 2004; 11 (Suppl 1): S18–S25.

    Article  CAS  Google Scholar 

  7. Jackson DA, Juranek S, Lipps HJ . Designing nonviral vectors for efficient gene transfer and long-term gene expression. Mol Ther 2006; 14: 613–626.

    Article  CAS  Google Scholar 

  8. Khalil IA, Kogure K, Akita H, Harashima H . Uptake pathways and subsequent intracellular trafficking in nonviral gene delivery. Pharmacol Rev 2006; 58: 32–45.

    Article  CAS  Google Scholar 

  9. Yamada T, Iwasaki Y, Tada H, Iwabuki H, Chuah MK, VandenDriessche T et al. Nanoparticles for the delivery of genes and drugs to human hepatocytes. Nat Biotechnol 2003; 21: 885–890.

    Article  CAS  Google Scholar 

  10. Mastrobattista E, van der Aa MA, Hennink WE, Crommelin DJ . Artificial viruses: a nanotechnological approach to gene delivery. Nat Rev Drug Discov 2006; 5: 115–121.

    Article  Google Scholar 

  11. Dauty E, Behr JP, Remy JS . Development of plasmid and oligonucleotide nanometric particles. Gene Ther 2002; 9: 743–748.

    Article  CAS  Google Scholar 

  12. Luo D, Han E, Belcheva N, Saltzman WM . A self-assembled, modular DNA delivery system mediated by silica nanoparticles. J Control Release 2004; 95: 333–341.

    Article  CAS  Google Scholar 

  13. Morita Y, Nakata K, Kim YH, Sekino T, Niihara K, Ikeuchi K . Wear properties of alumina/zirconia composite ceramics for joint prostheses measured with an end-face apparatus. Biomed Mater Eng 2004; 14: 263–270.

    CAS  PubMed  Google Scholar 

  14. Yih TC, Al Fandi M . Engineered nanoparticles as precise drug delivery systems. J Cell Biochem 2006; 97: 1184–1190.

    Article  CAS  Google Scholar 

  15. Kumar R, Cheang P, Khor KA . Radio frequency (RF) suspension plasma sprayed ultra-fine hydroxyapatite (HA)/zirconia composite powders. Biomaterials 2003; 24: 2611–2621.

    Article  CAS  Google Scholar 

  16. Kumar R, Prakash KH, Cheang P, Khor KA . Temperature driven morphological changes of chemically precipitated hydroxyapatite nanoparticles. Langmuir 2004; 20: 5196–5200.

    Article  CAS  Google Scholar 

  17. Nishikawa M, Takakura Y, Hashida M . Pharmacokinetics of plasmid DNA-based non-viral gene medicine. Adv Genet 2005; 53: 47–68.

    Article  CAS  Google Scholar 

  18. Read ML, Logan A, Seymour LW . Barriers to gene delivery using synthetic vectors. Adv Genet 2005; 53: 19–46.

    Article  CAS  Google Scholar 

  19. Mebius RE, Kraal G . Structure and function of the spleen. Nat Rev Immunol 2005; 5: 606–616.

    Article  CAS  Google Scholar 

  20. Fong CL, Hui KM . Generation of potent and specific cellular immune responses via in vivo stimulation of dendritic cells by pNGVL3-hFLex plasmid DNA and immunogenic peptides. Gene Ther 2002; 9: 1127–1138.

    Article  CAS  Google Scholar 

  21. Fong CL, Mok CL, Hui KM . Intramuscular immunization with plasmid coexpressing tumour antigen and Flt-3L results in potent tumour regression. Gene Ther 2006; 13: 245–256.

    Article  CAS  Google Scholar 

  22. O'Connor TP, Crystal RG . Genetic medicines: treatment strategies for hereditary disorders. Nat Rev Genet 2006; 7: 261–276.

    Article  CAS  Google Scholar 

  23. Cho YW, Kim JD, Park K . Polycation gene delivery systems: escape from endosomes to cytosol. J Pharm Pharmacol 2003; 55: 721–734.

    Article  CAS  Google Scholar 

  24. Hwang SJ, Davis ME . Cationic polymers for gene delivery: designs for overcoming barriers to systemic administration. Curr Opin Mol Ther 2001; 3: 183–191.

    CAS  PubMed  Google Scholar 

  25. Tan Y, Whitmore M, Li S, Frederik P, Huang L . LPD nanoparticles – novel nonviral vector for efficient gene delivery. Methods Mol Med 2002; 69: 73–81.

    CAS  PubMed  Google Scholar 

  26. Byun Y, Singh VK, Yang VC . Low molecular weight protamine: a potential nontoxic heparin antagonist. Thromb Res 1999; 94: 53–61.

    Article  CAS  Google Scholar 

  27. Tupin E, Poirier B, Bureau MF, Khallou-Laschet J, Vranckx R, Caligiuri G et al. Non-viral gene transfer of murine spleen cells achieved by in vivo electroporation. Gene Ther 2003; 10: 569–579.

    Article  CAS  Google Scholar 

  28. Pillarisetty VG, Katz SC, Bleier JI, Shah AB, DeMatteo RP . Natural killer dendritic cells have both antigen presenting and lytic function and in response to CpG produce IFN-gamma via autocrine IL-12. J Immunol 2005; 174: 2612–2618.

    Article  CAS  Google Scholar 

  29. Chaudhry UI, Katz SC, Kingham TP, Pillarisetty VG, Raab JR, Shah AB et al. In vivo overexpression of Flt3 ligand expands and activates murine spleen natural killer dendritic cells. FASEB J 2006; 20: 982–984.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This research was supported by a grant from the National Medical Research Council (NMRC) of Singapore. We thank Ms Kelly YW Chan for technical assistance.

Author information

Authors and Affiliations

  1. School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore

    K Tan, P Cheang & K M Hui

  2. Division of Cellular & Molecular Research, National Cancer Centre, Singapore

    I A W Ho, P Y P Lam & K M Hui

Authors
  1. K Tan
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. P Cheang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. I A W Ho
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. P Y P Lam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K M Hui
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K M Hui.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tan, K., Cheang, P., Ho, I. et al. Nanosized bioceramic particles could function as efficient gene delivery vehicles with target specificity for the spleen. Gene Ther 14, 828–835 (2007). https://doi.org/10.1038/sj.gt.3302937

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.gt.3302937

Keywords

This article is cited by

Search

Advanced search

Quick links