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Fe3O4-PEI-RITC Magnetic Nanoparticles with Imaging and Gene Transfer Capability: Development of a Tool for Neural Cell Transplantation Therapies

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ABSTRACT

Purpose

To develop Fe3O4-PEI-RITC magnetic nanoparticles with multimodal MRI-fluorescence imaging and transfection capability, for use in neural cell replacement therapies.

Methods

The Fe3O4-PEI-RITC MNPs were synthesised through a multi-step chemical grafting procedure: (i) Silanisation of MNPs with 3-iodopropyltrimethoxysilane; (ii) PEI coupling with iodopropyl groups on the MNP surface; and (iii) RITC binding onto the PEI coating. The cell labelling and transfection capabilities of these particles were evaluated in astrocytes derived from primary cultures.

Results

Fe3O4-PEI-RITC MNPs did not exert acute toxic effects in astrocytes (at ≤6 days). Cells showed rapid and extensive particle uptake with up to 100% cellular labelling observed by 24 h. MRI and microscopy studies demonstrate that the particles have potential for use in bimodal MR-fluorescence imaging. Additionally, the particles were capable of delivering plasmids encoding reporter protein (approximately 4 kb) to astrocytes, albeit with low efficiencies.

Conclusions

Multifunctional Fe3O4-PEI-RITC MNPs were successfully prepared using a multi-step synthetic pathway, with the PEI and RITC chemically bound onto the MNP surface. Their combined MR-fluorescence imaging capabilities with additional potential for transfection applications can provide a powerful tool, after further development, for non-invasive cell tracking and gene transfer to neural transplant populations.

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Abbreviations

CHN:

carbon, hydrogen, nitrogen

CNS:

central nervous system

DAPI:

4′,6-Diamidino-2-phenylindole

DLS:

dynamic Light Scattering

FITC:

fluorescein isothiocyanate

FTIR spectroscopy:

Fourier transform infrared spectroscopy

GFAP:

glial fibrillary acidic protein

GFP:

green fluorescent protein

MCT:

multiple comparison test

MNP:

magnetic nanoparticle

MRI:

magnetic resonance imaging

PBS:

phosphate-buffered saline

PEI:

polyethyleneimine

PVA:

polyvinyl alcohol

RITC:

rhodamine B isothiocyanate

RT:

room temperature

TEM:

transmission electron microscopy

TGA:

thermogravimetric analysis

XRD:

X-ray diffraction

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ACKNOWLEDGMENTS & DISCLOSURES

DMC is supported by a New Investigator Award from the British Biotechnology and Biological Sciences Research Council. The authors acknowledge EPSRC (EP/C511794) for financial support. We thank Dr. James Long (IOTA Nanosolutions) for the zeta potential measurements and Dr. Laurent Bouffier (now at Université Bordeaux) for his assistance with FTIR spectroscopy and Ms Karen Davies who performed the MRI measurements at the University of Manchester.

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Authors and Affiliations

  1. Chemical Engineering, School of Engineering and Physical Sciences, Heriot-Watt University, Edinburgh, EH14 4AS, UK

    Humphrey H. P. Yiu

  2. Institute for Science and Technology in Medicine, Keele University, Staffordshire, ST5 5BG, UK

    Mark R. Pickard & Divya M. Chari

  3. Department of Chemistry, University of Liverpool, Liverpool, L69 7ZD, UK

    Cristina I. Olariu & Matthew J. Rosseinsky

  4. Imaging Science, Proteomics & Genomics Research Group Manchester Academic Health Sciences Centre, University of Manchester, Oxford Road, Manchester, M13 9PT, UK

    Stephen R. Williams

Authors
  1. Humphrey H. P. Yiu
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  2. Mark R. Pickard
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  3. Cristina I. Olariu
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  4. Stephen R. Williams
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  5. Divya M. Chari
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  6. Matthew J. Rosseinsky
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Corresponding authors

Correspondence to Divya M. Chari or Matthew J. Rosseinsky.

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Yiu, H.H.P., Pickard, M.R., Olariu, C.I. et al. Fe3O4-PEI-RITC Magnetic Nanoparticles with Imaging and Gene Transfer Capability: Development of a Tool for Neural Cell Transplantation Therapies. Pharm Res 29, 1328–1343 (2012). https://doi.org/10.1007/s11095-011-0632-1

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  • DOI: https://doi.org/10.1007/s11095-011-0632-1

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