title: The in vivo radiosensitizing effect of gold nanoparticles based MRI contrast agents.
abstract: Owing to the high atomic number (Z) of gold element, the gold nanoparticles appear as very promising radiosensitizing agents. This character can be exploited for improving the selectivity of radiotherapy. However, such an improvement is possible only if irradiation is performed when the gold content is high in the tumor and low in the surrounding healthy tissue. As a result, the beneficial action of irradiation (the eradication of the tumor) should occur while the deleterious side effects of radiotherapy should be limited by sparing the healthy tissue. The location of the radiosensitizers is therefore required to initiate the radiotherapy. Designing gold nanoparticles for monitoring their distribution by magnetic resonance imaging (MRI) is an asset due to the high resolution of MRI which permits the accurate location of particles and therefore the determination of the optimal time for the irradiation. We recently demonstrated that ultrasmall gold nanoparticles coated by gadolinium chelates (Au@DTDTPA-Gd) can be followed up by MRI after intravenous injection. Herein, Au@DTDTPA and Au@DTDTPA-Gd were prepared in order to evaluate their potential for radiosensitization. Comet assays and in vivo experiments suggest that these particles appear well suited for improving the selectivity of the radiotherapy. The dose which is used for inducing similar levels of DNA alteration is divided by two when cells are incubated with the gold nanoparticles prior to the irradiation. Moreover, the increase in the lifespan of tumor bearing rats is more important when the irradiation is performed after the injection of the gold nanoparticles. In the case of treatment of rats with a brain tumor (9L gliosarcoma, a radio-resistant tumor in a radiosensitive organ), the delay between the intravenous injection and the irradiation was determined by MRI.
authors.forename: Imen
authors.initials: I
authors.lastname: Miladi
authors.forename: Christophe
authors.initials: C
authors.lastname: Alric
authors.forename: Sandrine
authors.initials: S
authors.lastname: Dufort
authors.forename: Pierre
authors.initials: P
authors.lastname: Mowat
authors.forename: Aurélie
authors.initials: A
authors.lastname: Dutour
authors.forename: Céline
authors.initials: C
authors.lastname: Mandon
authors.forename: Gautier
authors.initials: G
authors.lastname: Laurent
authors.forename: Elke
authors.initials: E
authors.lastname: Bräuer-Krisch
authors.forename: Nirmitha
authors.initials: N
authors.lastname: Herath
authors.forename: Jean-Luc
authors.initials: JL
authors.lastname: Coll
authors.forename: Marie
authors.initials: M
authors.lastname: Dutreix
authors.forename: François
authors.initials: F
authors.lastname: Lux
authors.forename: Rana
authors.initials: R
authors.lastname: Bazzi
authors.forename: Claire
authors.initials: C
authors.lastname: Billotey
authors.forename: Marc
authors.initials: M
authors.lastname: Janier
authors.forename: Pascal
authors.initials: P
authors.lastname: Perriat
authors.forename: Géraldine
authors.initials: G
authors.lastname: Le Duc
authors.forename: Stéphane
authors.initials: S
authors.lastname: Roux
authors.forename: Olivier
authors.initials: O
authors.lastname: Tillement
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D003287:Contrast Media; D006046:Gold; D006801:Humans; D008279:Magnetic Resonance Imaging; D053768:Metal Nanoparticles; D012516:Osteosarcoma / Q000175:diagnosis / Q000473:pathology; D011838:Radiation-Sensitizing Agents; D051381:Rats; D017207:Rats, Sprague-Dawley; D013154:Spleen / Q000166:cytology; D016019:Survival Analysis
chemical_list: D003287:Contrast Media; D011838:Radiation-Sensitizing Agents; D006046:Gold