The aim of this study was to achieve an efficient therapy against RET/PTC3 junction oncogene using siRNA technology. We first established RET/PTC3 expressing cell line, named RP3, from murine NIH/3T3 fibroblasts. Then siRNAs were designed and studied for the RET/PTC3 silencing effects, apoptosis and cell cycle regulation pathways. The most efficient siRNA RET/PTC3 was conjugated to squalene and the efficiency of the resulting nanoassemblies was validated in vitro before testing in preclinical experiments. Our results strongly suggest that siRNA RET/PTC3-SQ NPs could be accredited as a potential new pharmacological approach for papillary thyroid carcinoma with RET/PTC3 junction oncogene. This also demonstrates that the siRNA RET/PTC3 is still active; after bio-conjugation with squalene, due to modification of the passenger sense strand only and the use of an ester hydrolysable bond between the squalene moiety and the siRNA part. The discrepancy between in vitro and in vivo nanoparticles uptake and silencing efficiency is probably due to differences between the enzymatic contents found in vivo biological fluids and in culture conditions, the possible rationalization was discussed previously. In conclusion, the significance of siRNA RET/PTC3-SQ NPs have been demonstrated in preclinical studies for thyroid cancer therapy and further pharmacological and clinical investigations can be proceeded to set-in the remedy of thyroid carcinoma. Furthermore, in future, we desire to extend our investigations to other cancer pathologies carrying junction oncogene, so that the “squalenoylation” could be used as a generic platform for the administration and the transport of therapeutic siRNA. Combined exposure to fluoride and arsenic may result in more complicated adverse health effects than exposure to fluoride or arsenic alone. Many health hazards caused by fluoride and arsenic alone have been reported, but less has been reported about their joint effects on health. Furthermore, some results have been contradictory. For example, different joint actions, including independent, synergistic, and antagonistic effects, have been observed in different experimental studies. Therefore, further research is needed to reveal the interaction between fluoride and arsenic with regard to their toxic effects. Fluoride and arsenic are able to cross the blood-brain barrier or placental barrier and accumulate in the brain in rats and mice exposed to high concentrations of fluoride and arsenic. Some epidemiological studies have demonstrated that chronic exposure to fluoride and arsenic in drinking water is associated with lower child intelligence and impairments in cognitive and neurobehavioral function. However, relatively little information is available in the literatures about the association between fluoride-arsenic co-exposure and cognitive and neurobehavioral function in humans.