Challenges of combining gadolinium-based nanoparticles with low- and high-LET radiation IN THE treatment of head and neck squamous cell carcinoma

Communication oraleInternational audienc

Challenges of combining gadolinium-based nanoparticles with low- and high-LET radiation IN THE treatment of head and neck squamous cell carcinoma

Communication oraleInternational audienc

Biodistribution of ultrasmall gadolinium-based nanoparticles as theranostic agent : Application to brain tumors

International audienceGadolinium-based nanoparticles are novel objects with interesting physical properties, allowing their use for diagnostic and therapeutic applications. Gadolinium-based nanoparticles were imaged following intravenous injection in healthy rats and rats grafted with 9L gliosarcoma tumors using magnetic resonance imaging and scintigraphic imaging. Quantitative biodistribution using gamma-counting of each sampled organ confirmed that these nanoparticles were rapidly cleared essentially by renal excretion. Accumulation of these nanoparticles in 9L gliosarcoma tumors implanted in the rat brain was quantitated. This passive and long-duration accumulation of gadolinium-based nanoparticles in tumor, which is related to disruption of the blood–brain barrier, is in good agreement with the use of these nanoparticles as radiosensitizers for brain tumors

Effect of the nanoparticle synthesis method on dendronized iron oxides as MRI contrast agents

Aqueous suspensions of dendronized iron oxide nanoparticles (NPs) have been obtained after functionalization, with two types of dendrons, of NPs synthesized either by coprecipitation (leading to naked NPs in water) or by thermal decomposition (NPs in situ coated by oleic acid in an organic solvent). Different grafting strategies have been optimized depending on the NPs synthetic method. The size distribution, the colloidal stability in isoosmolar media, the surface complex nature as well as the preliminary biokinetic studies performed with optical imaging, and the contrast enhancement properties evaluated through in vitro and in vivo MRI experiments, have been compared as a function of the nature of both dendrons and NPs. All functionalized NPs displayed good colloidal stability in water, however the ones bearing a peripheral carboxylic acid function gave the best results in isoosmolar media. Whereas the grafting rates were similar, the nature of the surface complex depended on the NPs synthetic method. The in vitro contrast enhancement properties were better than commercial products, with a better performance of the NPs synthesized by coprecipitation. On the other hand, the NPs synthesized by thermal decomposition were more efficient in vivo. Furthermore, they both displayed good biodistribution with renal and hepatobiliary elimination pathways and no consistent RES uptake

Gadolinium based nanoparticles as radiosensitizing agents for radioresistant head and neck tumours

International audienceRadiotherapy is one of the main therapies for cancer, but it remains limited when tumours are radioresistant such glioblastoma, head and neck tumours, osteo and chondrosarcomas for example. Several strategies aiming at radiosensitizing these resistant tumours are under development. One of those relies on the use of high density nanoparticles, which once delivered into the tumour should deliver secondary radiations amplifying the radiotherapy efficiency. A previous reported study from our consortium showed that Gadolinium Based Nanoparticles (GBN) were able to induce a clonogenic death of SQ20B cells in culture (human head and neck carcinoma cells). The present study aimed at the demonstration of the in-vivo radiosensitizing effect of these GBN on SQ20B xenograft tumour. Radiation Therapy (RT) was performed using a biological X-Ray Irradiator (X-RAD 320) (Byfleet, Surrey) with 320 KV X-rays. The field of irradiation was adapted according to tumor volume by using an adjustable collimator positioned 35 cm from the animals. The dose rate was of 2 Gy.min-1. Four/five weeks after tumor grafting, mice with tumor volume less than 400 mm3 were randomly selected for radiotherapy 5 minutes after intratumoral (IT) injection of either GBN or saline. Four groups of rats were compared: IT injection of saline only (Control) (n = 9), GBN IT injection only (GBN injection) (n = 9), IT injection of saline + 10 Gy radiation (IR 10Gy) (n = 13), and IT injection of GBN + 10 Gy (IR 10Gy + GBN) (n = 10). Compared to the progressive and massive increase in tumor volume observed in the control groups (control and GBN injection groups), 10 Gy radiation stabilized tumor evolution between the second and the third week after radiation. The tumors then started to develop again with a growth curve similar to that of the control group. In contrast, the combination of GBN with 10 Gy radiation limited spectacularly the SQ20B tumors growth. At the end of week 6, the mean reduction in tumor volume in the IR 10Gy + GBN group, was of 626 and 388% (P = 0,003) compared, respectively, to the control and only irradiated tumors. Moreover, in the end of our therapy study, tumors have disappeared in two mice given 10 Gy with GBN treatment. Combined with the in-vitro study, the reported results demonstrate a major radiosensitizing effect of Gadolinium Based Nanoparticles on radioresistant tumours such as Head and Neck carcinomas