Synthesis and Evaluation of Novel Biocompatible Super-paramagnetic Iron Oxide Nanoparticles as Magnetic Anticancer Drug Carrier and Fluorescence Active Label - Université de Tours Access content directly
Journal Articles Journal of Physical Chemistry C Year : 2010

Synthesis and Evaluation of Novel Biocompatible Super-paramagnetic Iron Oxide Nanoparticles as Magnetic Anticancer Drug Carrier and Fluorescence Active Label

Andriy Shkilnyy
  • Function : Author
Emilie Munnier
Katel Hervé
  • Function : Author
Martin Soucé
  • Function : Author
Roland Benoit
Simone Cohen-Jonathan
  • Function : Author
Marie-Louise Saboungi
Pierre Dubois
  • Function : Author
Igor Chourpa

Abstract

We report a one-pot synthesis protocol for highly efficient and stable covalent binding of both the fluorescent drug doxorubicin (DOX) and the biocompatible polymer poly(ethylene glycol) (PEG) to the surface of superparamagnetic iron oxide nanoparticles (SPIONs). The final aim is to obtain a biocompatible, injectable nanosystem combining anticancer activity (magnetically targeted drug delivery) and nondestructive imaging of the treated cancer cells and tissues by means of fluorescence and magnetic resonance imaging (MRI). Our protocol employs silane and epoxide chemistry, which could also be useful to bind other molecules possessing a primary or secondary amine group, such as drugs, proteins, and fluorescent labels. The suspensions of SPIONs-DOX-PEG (iron concentration of 17 mg/L) obtained in this study are stable at physiological pH values. This stability coupled with the PEG surface neutrality makes these nanoparticles compatible with their application in vivo, via systemic administration. Efficient binding of DOX to the SPIONs surface via the amine group of the sugar moiety of the drug, i.e., outside of the aromatic pharmacophore-fluorophore, preserves the fluorescence activity of DOX. Confocal fluorescence spectral imaging of treated MCF7 cancer cells indicates that, in spite of the accumulation of SPIONs-DOX-PEG in the cytosol, only a minor fraction of the drug reaches the nucleus in 24 h. As a result, no in vitro cytotoxicity against MCF7 cancer cells was detected (the highest iron and drug concentrations were 2.7 mg/L and 8.1 µM, respectively). Interestingly, SPIONs-DOX particles noncoated with PEG were cytotoxic. We conclude that cellular enzymes can cleave the amine drug-particle linkage, but the PEG shell hinders the cleavage, possibly by sterical repulsion. Therefore, the developed chemistry is useful for stable coating of SPIONs with polymers and fluorescent labels, while an alternative strategy will be needed for more efficient drug release.
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Dates and versions

hal-03407003 , version 1 (28-10-2021)

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Andriy Shkilnyy, Emilie Munnier, Katel Hervé, Martin Soucé, Roland Benoit, et al.. Synthesis and Evaluation of Novel Biocompatible Super-paramagnetic Iron Oxide Nanoparticles as Magnetic Anticancer Drug Carrier and Fluorescence Active Label. Journal of Physical Chemistry C, 2010, 114 (13), pp.5850-5858. ⟨10.1021/jp9112188⟩. ⟨hal-03407003⟩
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