Ultrapure laser-synthesized Si-based nanomaterials for biomedical applications: in vivo assessment of safety and biodistribution.

Si/SiOx nanoparticles (NPs) produced by laser ablation in deionized water or aqueous biocompatible solutions present a novel extremely promising object for biomedical applications, but the interaction of these NPs with biological systems has not yet been systematically examined. Here, we present the first comprehensive study of biodistribution, biodegradability and toxicity of laser-synthesized Si-SiOx nanoparticles using a small animal model. Despite a relatively high dose of Si-NPs (20 mg/kg) administered intravenously in mice, all controlled parameters (serum, enzymatic, histological etc.) were found to be within safe limits 3 h, 24 h, 48 h and 7 days after the administration. We also determined that the nanoparticles are rapidly sequestered by the liver and spleen, then further biodegraded and directly eliminated in urine without any toxicity effects. Finally, we found that intracellular accumulation of Si-NPs does not induce any oxidative stress damage. Our results evidence a huge potential in using these safe and biodegradable NPs in biomedical applications, in particular as vectors, contrast agents and sensitizers in cancer therapy and diagnostics (theranostics).

Efficacy of a combination of pemetrexed and multiple redo-surgery in an 11-year-old girl with a recurrent multifocal abdominal mesothelioma.

We report the case of an 11-year-old girl with a recurrent progressive locally advanced abdominal mesothelioma. First, there was an incomplete surgical resection without any complementary chemotherapy, followed by a slow progression of the disease. Three years later, after two macroscopically complete surgical resections of peritoneal and ovarian tumors, she failed to respond to treatment with gemcitabin-carboplatin and gemcitabin-cisplatin, and developed splenic tumors and large multicystic hepatic tumors. She was then treated with pemetrexed. The schedule of chemotherapy was pemetrexed 400 mg intravenously plus cisplatin 60 mg once every 3 weeks associated with folic acid and vitamin B12. The tumor reduction was evaluated with positron emission tomography scan and tomodensitometry every three courses. Chemotherapy tolerance was good apart from a grade III neutropenia at the second course, a fever of unknown origin at the fifth course and a grade III thrombocytopenia at the sixth course. As tolerance and clinical responses were good, pemetrexed posology was increased up to 10%. After six courses, hepatic and splenic lesion tumors were initially diminished and then stablilized. Thus, a surgical resection was attempted: a first surgery followed by a second one 3 days later allowed completion of a difficult left hepatectomy, and resection of the hilum and splenic tumors. Fourteen months after the surgery, the girl remained in partial remission with stable disease. So far, pemetrexed associated with cisplatin revealed a good tolerance and promising results regarding its antitumoral efficacy in a progressive metastatic abdominal mesothelioma in childhood.