Intracellular synchrotron nanoimaging and DNA damage/genotoxicity screening of novel lanthanide-coated nanovectors.

David J Lewis 1 Christopher Bruce 2 Sylvain Bohic 3 Peter Cloetens 4 Stephen P Hammond 1 Darren Arbon 2 Sarah Blair-Reid 2 Zoe Pikramenou 1, * Boris Kysela 2
* Auteur correspondant
1 School of Chemistry
2 Clinical & Experimental Medicine
3 GIN - Grenoble Institut des Neurosciences
4 ESRF - European Synchrotron Radiation Facility
Abstract : AIMS: In cancer therapy, research has focused on the development of nanocarriers that can aid diagnosis, deliver therapeutic agents and monitor treatment progress. This study introduces high-resolution synchrotron x-ray fluorescence microscopy (SR-XFM) to investigate intracellular localization of novel lanthanide-coated nanoparticles in human cells and their genotoxicity screening after internalization. MATERIALS & METHODS: Noble metal nanoparticles coated with cerium and luminescent europium complexes have been developed as platforms for bioimaging and potential biodelivery applications. The intracellular distribution after internalization has been analyzed by ultrasensitive SR-XFM and genotoxicity evaluated using γ-H2AX DNA damage foci phosphorylation assay. RESULTS: We demonstrate the unprecedented capability of SR-XFM for extremely sensitive nanoimaging and intracellular elemental distribution analysis of noble metal nanoparticles in cells. Furthermore, we show that, depending on the charge of the coating complex and the presence of the DNA cargo, the internalization of functionalized nanoparticles by human fibroblasts can cause elevated levels of DNA damage detected by histone H2AX phosphorylation. CONCLUSION: The variable genotoxic impact of newly designed nanovectors emphasizes the need for careful and comprehensive testing of biological responses of all new nanoconstructs intended for future clinical applications. This can be greatly facilitated by SR-XFM nanoimaging of nanoparticles in cells at very low concentrations.
Keywords : DNA damage functionalized nanovector lanthanide nanoimaging nanoparticle genotoxicity synchrotron x-ray fluorescence microscopy
Type de document :
Article dans une revue
Nanomedicine, Future Medicine, 2010, 5 (10), pp.1547-57. 〈10.2217/nnm.10.96〉
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http://www.hal.inserm.fr/inserm-00589259
Contributeur : Raphael Serduc <>
Soumis le : jeudi 28 avril 2011 - 12:51:20
Dernière modification le : jeudi 1 février 2018 - 01:12:05

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David J Lewis, Christopher Bruce, Sylvain Bohic, Peter Cloetens, Stephen P Hammond, et al.. Intracellular synchrotron nanoimaging and DNA damage/genotoxicity screening of novel lanthanide-coated nanovectors.. Nanomedicine, Future Medicine, 2010, 5 (10), pp.1547-57. 〈10.2217/nnm.10.96〉. 〈inserm-00589259〉

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