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.

Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications

Abstract

Many nanosized particulate systems are being developed as intravascular carriers to increase the levels of therapeutic agents delivered to targets, with the fewest side effects1,2. The surface of these carriers is often functionalized with biological recognition molecules for specific, targeted delivery. However, there are a series of biological barriers in the body3,4,5 that prevent these carriers from localizing at their targets at sufficiently high therapeutic concentrations5,6. Here we show a multistage delivery system that can carry, release over time and deliver two types of nanoparticles into primary endothelial cells. The multistage delivery system is based on biodegradable and biocompatible mesoporous silicon particles that have well-controlled shapes, sizes and pores. The use of this system is envisioned to open new avenues for avoiding biological barriers and delivering more than one therapeutic agent to the target at a time, in a time-controlled fashion.

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

Relevant articles

Open Access articles citing this article.

Access options

Buy article

Get time limited or full article access on ReadCube.

$32.00

All prices are NET prices.

Figure 1: SEM images of a mesoporous silicon particle.
Figure 2: Flow cytometry and fluorescence microscopy of loading of Q-dots and PEG-FITC-SWNTs into mesoporous silicon.
Figure 3: Time-dependent loading and release of S2NPs.
Figure 4: Simultaneous loading and release of Q-dots and PEG-FITC-SWNTs in porous silicon particles.
Figure 5: Intracellular internalization of S2NPs delivered by S1MPs.

References

  1. Brannon-Peppas, L. & Blanchette, J. O. Nanoparticle and targeted systems for cancer therapy. Adv. Drug Deliv. Rev. 56, 1649–1659 (2004).

    CAS  Article  Google Scholar 

  2. Yezhelyev, M. V. et al. Emerging use of nanoparticles in diagnosis and treatment of breast cancer. Lancet Oncol. 7, 657–667 (2006).

    CAS  Article  Google Scholar 

  3. Ferrari, M. Nanovector therapeutics. Curr. Opin. Chem. Biol. 9, 343–346 (2005).

    CAS  Article  Google Scholar 

  4. Sakamoto, J., Annapragada, A., Decuzzi, P. & Ferrari, M. Antibiological barrier nanovector technology for cancer applications. Expert Opin. Drug Deliv. 4, 359–369 (2007).

    CAS  Article  Google Scholar 

  5. Ferrari, M. Cancer nanotechnology: opportunities and challenges. Nature Rev. Cancer 5, 161–171 (2005).

    CAS  Article  Google Scholar 

  6. Eckelman, W. C. & Mathis, C. A. Targeting proteins in vivo: In vitro guidelines. Nucl. Med. Biol. 33, 161–164 (2006).

    CAS  Article  Google Scholar 

  7. Lin, M. Z., Teitell, M. A. & Schiller, G. J. The evolution of antibodies into versatile tumor-targeting agents. Clin. Cancer Res. 11, 129–138 (2005).

    CAS  Google Scholar 

  8. Farokhzad, O. C., Karp, J. M. & Langer, R. Nanoparticle–aptamer bioconjugates for cancer targeting. Expert Opin. Drug Deliv. 3, 311–324 (2006).

    CAS  Article  Google Scholar 

  9. Torchilin, V. P. Multifunctional nanocarriers. Adv. Drug Deliv. Rev. 58, 1532–1555 (2006).

    CAS  Article  Google Scholar 

  10. Shuvaev, V. V. et al. Factors modulating the delivery and effect of enzymatic cargo conjugated with antibodies targeted to the pulmonary endothelium. J. Controlled Release 118, 235–244 (2007).

    CAS  Article  Google Scholar 

  11. Medina, O. P., Zhu, Y. & Kairemo, K. Targeted liposomal drug delivery in cancer. Curr. Pharm. Des. 10, 2981–2989 (2004).

    CAS  Article  Google Scholar 

  12. Pierres, A., Benoliel, A.-M., Zhu, C. & Bongrand, P. Diffusion of microspheres in shear flow near a wall: use to measure binding rates between attached molecules. Biophys. J. 81, 25–42 (2001).

    CAS  Article  Google Scholar 

  13. Decuzzi, P., Lee, S., Bhushan, B. & Ferrari, M. A theoretical model for the margination of particles within blood vessels. Ann. Biomed. Eng. 33, 179–190 (2005).

    CAS  Article  Google Scholar 

  14. Decuzzi, P. F. & Ferrari, M. Fantastic voyages. Mech. Eng. 128, 24–27 (2006).

    Article  Google Scholar 

  15. Decuzzi, P., Lee, S., Decuzzi, M. & Ferrari, M. Adhesion of microfabricated particles on vascular endothelium: a parametric analysis. Ann. Biomed. Eng. 32, 793–802 (2004).

    Article  Google Scholar 

  16. Canham, L. T. et al. Derivatized mesoporous silicon with dramatically improved stability in simulated human blood plasma. Adv. Mater. 11, 1505–1507 (1999).

    CAS  Article  Google Scholar 

  17. Bayliss, S. C., Heald, R., Fletcher, D. I. & Buckberry, L. D. The culture of mammalian cells on nanostructured silicon. Adv. Mater. 11, 318–321 (1999).

    CAS  Article  Google Scholar 

  18. Chin, V., Collins, B. E., Sailor, M. J. & Bhatia, S. N. Compatibility of primary hepatocytes with oxidized nanoporous silicon. Adv. Mater. 13, 1877–1880 (2001).

    CAS  Article  Google Scholar 

  19. Canham, L. T. Bioactive silicon structure fabrication through nanoetching techniques. Adv. Mater. 7, 1033–1037 (1995).

    CAS  Article  Google Scholar 

  20. Foraker, A. B. et al. Microfabricated porous silicon particles enhance paracellular delivery of insulin across intestinal caco-2 cell monolayers. Pharm. Res. 20, 110–116 (2003).

    CAS  Article  Google Scholar 

  21. Salonen, J. et al. Mesoporous silicon microparticles for oral drug delivery: Loading and release of five model drugs. J. Controlled Release 108, 362–374 (2005).

    CAS  Article  Google Scholar 

  22. Thomas, J. C., Pacholski, C. & Sailor, M. J. Delivery of nanogram payloads using magnetic porous silicon microcarriers. Lab Chip 6, 782–787 (2006).

    CAS  Article  Google Scholar 

  23. Stewart, M. P. & Buriak, J. M. Chemical and biological applications of porous silicon technology. Adv. Mater. 12, 859–869 (2000).

    CAS  Article  Google Scholar 

  24. Song, J. H. & Sailor, M. J. Chemical modification of crystalline porous silicon surfaces. Comments Inorg. Chem. 21, 69–84 (1999).

    CAS  Article  Google Scholar 

  25. Wang, Y. & Ferrari, M. Surface modification of micromachined silicon filters. J. Mater. Sci. 35, 4923–4930 (2000).

    CAS  Article  Google Scholar 

  26. Decuzzi, P. & Ferrari, M. The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials 27, 5307–5314 (2006).

    CAS  Article  Google Scholar 

  27. Lasic, D. D., Martin, F. J., Gabizon, A., Huang, S. K. & Papahadjopoulos, D. Sterically stabilized liposomes: a hypothesis on the molecular origin of the extended circulation times. Biochim. Biophys. Acta. 1070, 187–192 (1991).

    CAS  Article  Google Scholar 

  28. Hirsch, L. R. et al. Nanoshell-mediated near-infrared thermal therapy of tumours under magnetic resonance guidance. Proc. Natl Acad. Sci. USA 100, 13549–13554 (2003).

    CAS  Article  Google Scholar 

  29. Akin, D. et al. Bacteria-mediated delivery of nanoparticles and cargo into cells. Nature Nanotechn. 2, 441–449 (2007).

    CAS  Article  Google Scholar 

  30. Kim, S. et al. Near-infrared fluorescent type II quantum dots for sentinel lymph node mapping. Nature Biotechnol. 22, 93–97 (2004).

    CAS  Article  Google Scholar 

  31. Corot, C., Robert, P., Idee, J.-M. & Port, M. Recent advances in iron oxide nanocrystal technology for medical imaging. Adv. Drug Deliv. Rev. 58, 1471–1504 (2006).

    CAS  Article  Google Scholar 

  32. Kam, N. W. S., O'Connell, M., Wisdom, J. A. & Dai, H. Carbon nanotubes as multifunctional biological transporters and near-infrared agents for selective cancer cell destruction. Proc. Natl Acad. Sci. USA 102, 11600–11605 (2005).

    CAS  Article  Google Scholar 

Download references

Acknowledgements

We thank the University of Texas at Austin for the use of the semiconductor cleanroom facilities, M. Landry for excellent graphical support, A. Jimenez for laboratory assistance, and T. Tanaka and B. Godin for helpful suggestions. These studies were supported by the following grants: DoDW81XWH-04-2-0035 Project 16 (M.F., M.C., X.L., E.T., R.B.), NASA SA23-06-017 (M.F., M.C., X.L., R.B., E.T., J.T., A.L., B.K.P.), State of Texas, Emerging Technology Fund (M.F., X.L., R.B., K.P.), and the National Institutes of Health (NIH) NCI 1R21CA1222864-01 (M.F., M.C., F.R.). The authors would like to recognize the contributions and support from the Alliance for NanoHealth (ANH).

Author information

Authors and Affiliations

Authors

Contributions

E.T. and M.F. conceived and designed all the experiments. E.T. and K.P. performed the loading and release experiments. E.T. performed the fluorescence and confocal microscopy, the multiple loading and releasing experiments and the delivery experiments on HUVEC cells. R.B. made the chemical modifications to particles and measured the zeta potential values. X.L. and M.C. made the porous silicon particles, conducted the SEM imaging and the BET analysis. A.L. and B.K.P. made and characterized the PEG-FITC-SWNTs under the guidance of J.T.. P.D. developed the mathematical modeling and E.T., M.F. and F.R. discussed the interpretation of results. E.T. wrote the draft paper and all co-authors helped in the revision of the paper.

Corresponding author

Correspondence to Mauro Ferrari.

Ethics declarations

Competing interests

Commercialization rights on intellectual property presented in this paper have been acquired by Leonardo Biosystems Inc., from the title holder, the University of Texas Health Science Center in Houston. M.F. is the founding scientist of Leonardo Biosystems, and hereby discloses a financial interest in the company.

Supplementary information

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Tasciotti, E., Liu, X., Bhavane, R. et al. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotech 3, 151–157 (2008). https://doi.org/10.1038/nnano.2008.34

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nnano.2008.34

Further reading

Search

Quick links

Find nanotechnology articles, nanomaterial data and patents all in one place. Visit Nano by Nature Research