Abstract
AGuIX® are sub-5 nm nanoparticles made of a polysiloxane matrix and gadolinium chelates. This nanoparticle has been recently accepted in clinical trials in association with radiotherapy. This review will summarize the principal preclinical results that have led to first in man administration. No evidence of toxicity has been observed during regulatory toxicity tests on two animal species (rodents and monkeys). Biodistributions on different animal models have shown passive uptake in tumours due to enhanced permeability and retention effect combined with renal elimination of the nanoparticles after intravenous administration. High radiosensitizing effect has been observed with different types of irradiations in vitro and in vivo on a large number of cancer types (brain, lung, melanoma, head and neck…). The review concludes with the second generation of AGuIX nanoparticles and the first preliminary results on human.
Highlights
Radiosensitization by nanomaterials has attracted significant interests in the last decade
Contemporary RT techniques, such as intensity-modulated radiation therapy, volumetric-modulated arc therapy and image-guided radiation therapy (IGRT) have significantly improved tumour targeting,[4] while another potential approach to improve therapeutic index is the use of radiosensitizers
In vitro In particular, the radiosensitizing effects of AGuIX NPs on clinical irradiators at 6 MV have been demonstrated in a number of cell lines including cervical carcinoma – HeLa (SER4Gy = 1.3; Dose Enhancement Factor (DEF) = 1.2),[57] glioblastoma–U87MG (SER from 1.10 to 1.50 for concentrations ranging from 0.1 to 0.5 mM)[58] and pancreatic adenocarcinoma–panc[1] (DEF = 1.30) (Figure 8).[46,59]
Summary
AGuIX® from bench to bedside—Transfer of an ultrasmall theranostic gadolinium-based nanoparticle to clinical medicine. 1,2François Lux, PhD, 2,3Vu Long Tran, PhD, 2Eloïse Thomas, PhD, 1Sandrine Dufort, PdD, 2Fabien Rossetti, 2Matteo Martini, PhD, 4Charles Truillet, Ph D, 1Tristan Doussineau, Ph D, 2Guillaume Bort, Ph D, 5Franck Denat, Pr, 6Frédéric Boschetti, Ph D, 7Goran Angelovski, Ph D, 8Alexandre Detappe, Ph D, 9Yannick Crémillieux, Ph D, 10,11,12,13Nathalie Mignet, Ph D, 10,11,12,13Bich-Thuy Doan, Ph D, 14,15Benoit Larrat, Ph D, 14,15Sébastien Meriaux, Ph D, 16Emmanuel Barbier, Ph D, 17Stéphane Roux, Pr, 18Peter Fries, Ph D, 18Andreas Müller, Ph D, 19,20Marie-Caline Abadjian, Ph D, 19,20Carolyn Anderson, Pr, 21Emmanuelle Canet-Soulas, Pr, 22Penelope Bouziotis, Pr, 23Muriel Barberi-Heyob, Pr, 24Céline Frochot, Ph D, 25Camille Verry, Ph D, 25Jacques Balosso, Pr, 26Michael Evans, Ph D, 27Jacqueline Sidi-Boumedine, Ph D, 27,28Marc Janier, Pr, 29Karl Butterworth, Ph D, 29Stephen McMahon, Ph D, 29Kevin Prise, Pr, 30Marie-Thérèse Aloy, Ph D, 30Dominique Ardail, Ph D, 30Claire Rodriguez-Lafrasse, Pr, 31Erika Porcel, Ph D, 31Sandrine Lacombe, Pr, 8Ross Berbeco, Ph D, 32,33,34,35Awatef Allouch, Ph D, 32,33,34,35Jean-Luc Perfettini, Pr, 36,37,38,39Cyrus Chargari, Ph D, 38,39Eric Deutsch, Pr, 1Géraldine Le Duc, Ph D and 1,2Olivier Tillement, Pr. Lyon, Oullins, France 22Institute of Nuclear & Radiological Sciences & Technology, Energy & Safety, National Center forScientific Research "Demokritos", Aghia.
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