Contribution (Oral)
Synthesis of a dye-functionalized hydrophilic dendron dedicated to surface engineering of iron
oxide nanoparticles for magneto-optical detection of the sentinel node in early breast cancer
Marie Kueny-Stotz, Lai Truong Phuoc, François-Xavier Blé, Franklin Tellier, Patrick Poulet, Geneviève
Pourroy, Sylvie Begin-Colin, Delphine Felder-Flesch
a
Institut de Physique et Chimie des Matériaux de Strasbourg (IPCMS), UMR CNRS/ULP 7504, 23 rue
du Loess, F-67034 Strasbourg, France.
b Laboratoire d’Imagerie et de Neurosciences Cognitives, Institut de Physique Biologique, Faculté de
Médecine, 4 rue Kirschleger, F-67085 Strasbourg, France.
kueny@ipcms.u-strasbg.fr
Since the last ten years, superparamagnetic iron oxide nanoparticles (SPIO NPs) of small sizes
(between 10 and 40 nm) have become of great interest in the field of biomedicine.1 Indeed, decorating
these nano-objects with multifunctional and biocompatible organic ligands can lead to powerful
applications, which include notably Magnetic Resonance Imaging (MRI) contrast enhancement and
targeted cancer therapy by sentinel node detection. If polymers have long been employed to coat the
surface of SPIO NPs,2 dendrons are nowadays more and more used, due to their great advantages
(monodispersity, easy change of the characteristics by enhancing the generation,..). 3 In our team, which
has been interested for several years in surface engineering of SPIO NPs dedicated to MRI contrast
enhancement,4 new attempts to develop original and never-encountered dendronized SPIO NPs have
recently been investigated in the field of cancer therapy and especially in the treatment of breast cancer
through sentinel node (any node receiving lymph drainage from the tumour site and containing most
likely malignancy if the tumour has metastasized) detection. Most teams using sentinel node biopsy in
the treatment of breast cancer inject either radioactive colloid ( 99mTc-labelled RuS)5 or Patent Blue dye6
in the periareolar area to label the lymph node system for its per-operative detection. The detection is
done by a gamma probe or visual colour detection respectively. If radioisotope injection is widely used
today in the most advanced countries, new strategies using non-nuclear detection are also investigated,
and in this context, we decided to develop a new and original project based on dendritic magnetic iron
oxide nanoparticles bearing a blue dye for magneto-optical detection (scheme 1).
In this approach, suspensions of magnetic nanoparticles of size between 10 and 40 nm have been
prepared. A dendritic structure has been designed to surround the nanoparticles. This molecule, which
holds three key-functionalities,
(i) a phosphonate anchor to link covalently the nanoparticles,
(ii) PEG-groups ensuring the hydrophilicity and the biocompatibility of the final nano-object, and
(iii) a blue dye allowing optical detection, has been prepared in 14 steps.
We will discuss the synthesis of this specific dendron, explain its grafting on the iron oxide nanoparticles
and outline the dendronized-nanoparticles colloidal suspension properties. Finally, some first in vivo
magneto-optical detection results will be presented.
Acknowledgement: European Community's Seventh Framework Programme (FP7 2007-2013) under
grant agreement nr NMP3-SL-2008-214032.
References
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Contribution (Oral)
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Scheme 1
Dendritic and blue dye-derivatized magnetic iron oxide nanoparticles