AGuIX: a new class of multimodal ultra small gadolinium based nanoparticles for theranostic applications

Full text of publication follows. A new type of sub-5-nanometer ultra small gadolinium nano-probe has recently been developed by our team for biomedical applications. The AGuIX nanoparticles are composed of a polysiloxane matrix and surrounded by gadolinium chelates covalently grafted at the surface of the inorganic matrix [Ref.1]. They have been injected in healthy animals, they are eliminated by the kidneys and can be detected by four complementary imaging techniques (MRI, scintigraphy, optical imaging and X Ray tomography) [Ref.2]. Despite their small sizes, the nanoparticles are also concentrated in the tumors by enhanced permeability and retention (EPR) effect. The grafting of cRGDfK on the nanoparticles has been performed thanks to classical carbodiimide chemistry. The grafted nanoparticles present a high affinity (shown by flow cytometry and fluorescence microscopy) for cells expressing α_vβ₃ integrins in comparison with the same nanoparticles grafted with cRADfK as negative controls. The grafted nanoparticles were also injected in gliosarcoma tumor bearing mice and a higher signal in fluorescence was observed for cRGDfK grafted nanoparticles. Due to the presence of gadolinium (a high Z element), the AGuIX nanoparticles can also be used as radiosensitizer. A high radiosensitizing effect has been observed in vitro using different types of irradiation on radioresistant cells [Ref.3]. Finally the nanoparticles have been injected in 9L gliosarcoma bearing rats, the nanoparticles have been monitored by MRI to determine the best moment for irradiation (i. e. the higher concentration of nanoparticles in the tumor with the lowest concentration in the surrounding healthy tissue). The irradiation by MRT lead to a huge increase of the lifespan of the tumor bearing rats. References: [1] A. Mignot et al. Chem. Eur. J., 2013, DOI: 10.1002/chem.201203003; [2] F. Lux et al., Angew. Chem. Int. Ed., 2011, 123, 12507-12511; [3] P. Mowat et al., J. Nanosci. Nanotechnol., 2011, 11, 7833-7839; [4] G. Le Duc et al., ACS Nano, 2011, 5, 9566. (authors)