Skip to main content
SpringerLink
Log in

Functionalization and peptide-based delivery of magnetic nanoparticles as an intracellular MRI contrast agent

  • Original Article
  • Published:
JBIC Journal of Biological Inorganic Chemistry Aims and scope Submit manuscript

Abstract

We report the development of functionalized superparamagnetic iron oxide nanoparticles with a PEG-modified, phospholipid micelle coating, and their delivery into living cells. The size of the coated particles, as determined by dynamic light scattering and electron microscopy, was found to be between 12 and 14 nm. The PEG-phospholipid coating resulted in high water solubility and stability, and the functional groups of modified PEG allowed for bioconjugation of various moieties, including a fluorescent dye and the Tat peptide. Efficient delivery of the functionalized nanoparticles into living cells was confirmed by fluorescence microscopy, relaxation time measurements, and magnetic resonance imaging (MRI). This demonstrates the feasibility of using functionalized magnetic nanoparticles with uniform (~10 nm) sizes as an MRI contrast agent for intracellular molecular imaging in deep tissue. These micelle-coated iron oxide nanoparticles offer a versatile platform for conjugation of a variety of moieties, and their small size confers advantages for intracellular molecular imaging with minimal perturbation.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2A, B
Fig. 3
Fig. 4A, B
Fig. 5A, B

Similar content being viewed by others

Abbreviations

CPP:

cell penetrating peptide

CPMG:

Carr–Purcell–Meiboom–Gill spin-echo method

CTAB:

cetyltrimethylammonium bromide

DLS:

dynamic light scattering

DMEM:

Dulbecco’s modified Eagle’s medium

DSPE:

1,2-distearoyl-sn-glycero-3-phosphoethanolamine

FCS:

fetal calf serum

FGM-2:

fibroblast growth medium 2

HDF:

human dermal fibroblast

HS:

horse serum

MDBK:

Madin–Darby bovine kidney

MIONs:

superparamagnetic iron oxide nanoparticles

mMIONs:

micelle-coated MIONs

MRI:

magnetic resonance imaging

PBS:

phosphate-buffered saline

PEG:

poly(ethylene glycol)

SPDP:

N-succinimidyl 3-(2-pyridyldithio)propionate

TCEP:

tris(2-carboxyethyl)phosphine hydrochloride

TEM:

transmission electron microscopy

References

  1. Dyal A, Loos K, Noto M, Chang SW, Spagnoli C, et al. (2003) J Am Chem Soc 125:1684–1685

    Article  CAS  PubMed  Google Scholar 

  2. Zhao M, Kircher MF, Josephson L, Weissleder R (2002) Bioconjug Chem 13:840–844

    Article  CAS  PubMed  Google Scholar 

  3. Bulte JWM, Douglas T, Witwer B, Zhang S-C, Strable E, et al. (2001) Nat Biotechnol 19:1141–1147

    Article  CAS  PubMed  Google Scholar 

  4. Lewin M, Carlesso N, Tung CH, Tang XW, Cory D, et al. (2000) Nat Biotechnol 18:410–414

    Article  CAS  PubMed  Google Scholar 

  5. Dressman D, Yan H, Traverso G, Kinzler KW, Vogelstein B (2003) Proc Natl Acad Sci USA 100:8817–8822

    Article  CAS  PubMed  Google Scholar 

  6. Lanza GM, Abendschein DR, Yu X, Winter PM, Karukstis KK, et al. (2002) Acad Radiol (Suppl 2) 9:S330–S331

  7. Butler JP, Kelly SM (1998) Biorheology 35:193–209

    Article  CAS  PubMed  Google Scholar 

  8. Perez JM, O’Loughin T, Simeone FJ, Weissleder R, Josephson L (2002) J Am Chem Soc 124:2856–2857

    Article  CAS  PubMed  Google Scholar 

  9. Liu Q, Xu Z (1995) Langmuir 12:4617–4622

    Google Scholar 

  10. Yee C, Kataby G, Ulman A, Prozorov T, White H, et al. (1999) Langmuir 15:7111–7115

    Article  CAS  Google Scholar 

  11. Harris LA, Goff JD, Carmichael AY, Riffle JS, Harburn JJ, et al. (2003) Chem Mater 15:1367–1377

    Article  CAS  Google Scholar 

  12. Burke NAD, Stover HDH, Dawson FP (2002) Chem Mater 14:4752–4761

    Article  CAS  Google Scholar 

  13. Santra S, Tapec R, Theodoropoulou N, Dobson J, Hebard A, Tan W (2001) Langmuir 17:2900–2906

    Article  CAS  Google Scholar 

  14. Lu Y, Yin Y, Mayers BT, Xia Y (2002) Nano Letters 2:183–186

    Article  CAS  Google Scholar 

  15. Butterworth MD, Illum L, Davis SS (2001) Colloids Surf A 179:93–102

    Article  CAS  Google Scholar 

  16. Kim DK, Mikhaylova M, Zhang Y, Muhammed M (2003) Chem Mater 15:1617–1627

    Article  CAS  Google Scholar 

  17. Jones M, Leroux J (1999) Eur J Pharmacol Biopharmacol 48:101–111

    Article  CAS  Google Scholar 

  18. Perkins WR, Ahmad I, Li X, Hirsh DJ, Masters GR, et al. (2000) Int J Pharmacol 200:27–39

    Article  CAS  Google Scholar 

  19. Torchilin VP (2002) Adv Drug Deliv Rev 54:235–252

    Article  CAS  PubMed  Google Scholar 

  20. Torchilin VP, Lukyanov AN, Gao Z, Papahadjopoulos-Sternberg B (2003) Proc Natl Acad Sci USA 100:6039–6044

    Article  CAS  PubMed  Google Scholar 

  21. Dubertret B, Skourides P, Norris DJ, Noireaux V, Brivanlou AH, Libchaber A (2002) Science 298:1759–1762

    Article  CAS  PubMed  Google Scholar 

  22. Gref R, Couvreur P, Barratt G, Mysiakine E (2003) Biomaterials 24:4529–4537

    Article  CAS  PubMed  Google Scholar 

  23. Braginskaya TG, Dobitchin PD, Ivanova MA, Klyubin VV, Lomakin AV, et al. (1983) Phys Scr 28:73–79

    CAS  Google Scholar 

  24. Atkins RC (1975) J Chem Educ 52:550

    CAS  PubMed  Google Scholar 

  25. Feltin N, Pileni MP (1997) Langmuir 13:3927–3933

    Article  CAS  Google Scholar 

  26. Seip CT, O’Connor CJ (1999) NanoStruct Mater 12:183–186

    Article  Google Scholar 

  27. Torchilin VP, Levchenko TS, Rammohan R, Volodina N, Papahadjopoulos-Sternberg B, D’Souza GG (2003) Proc Natl Acad Sci USA 100:1972–1977

    Article  CAS  PubMed  Google Scholar 

  28. Torchilin VP, Rammohan R, Weissig V, Levchenko TS (2001) Proc Natl Acad Sci USA 98:8786–8791

    Article  CAS  PubMed  Google Scholar 

  29. Haacke EM, Brown RW, Thompson MR, Venkatesan R (1999) Magnetic resonance imaging: physical principles and sequence design. Wiley, New York

    Google Scholar 

Download references

Acknowledgements

The authors thank Dr. Charles O’Connor and his group (Daniela Carunta and Brian Cushing) for providing magnetic nanoparticles, Igor Vilfin and Nicholas Hud for their help with DLS measurements, and Hong Yi for her assistance with electron microscopy. This work was supported by DARPA/AFOSR (F49620–03–1-0320).

Author information

Authors and Affiliations

  1. Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, Atlanta, GA , 30332, USA

    N. Nitin, L. E. W. LaConte, O. Zurkiya, X. Hu & G. Bao

Authors
  1. N. Nitin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. L. E. W. LaConte
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. O. Zurkiya
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. X. Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. G. Bao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to G. Bao.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Nitin, N., LaConte, L.E.W., Zurkiya, O. et al. Functionalization and peptide-based delivery of magnetic nanoparticles as an intracellular MRI contrast agent. J Biol Inorg Chem 9, 706–712 (2004). https://doi.org/10.1007/s00775-004-0560-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00775-004-0560-1

Keywords

Search

Navigation