Efficacy of functionalized silica nanoparticles with flufenamic acid in protecting normal cells from Radiation Bystander Effect

Cancer is one of the main causes of death and morbidity in the world, thus, making it one of the most studied diseases. There are three treatments available to cure or at least shrink tumor size: surgery, chemotherapy and radiotherapy. These treatments can be used separate or a combination of it. All these treatments have side effects and 50% of cases require radiation therapy. Some research show that cells not hit by main radiation beam although they respond as if they were directly irradiated in a phenomenon known as Radiation Bystander Effect (RBE). This effect takes place due to communication between cells through Gap-junction (GJ) which leads to side effects. It is possible to inhibit the RBE with drugs that block the GJ with flufenamic acid (FFA). The lack of selectivity of FFA can be overcome by its incorporation on to nanoparticles. The leaky blood vessels of the tumor allow nanoparticles up to 200 nm of diameter to pass through into the interstitial space where they are retained by a phenomenon known as Enhanced Permeability and Retention (EPR) (PADERA et al., 2004). Given that there is a lack of studies which investigate the use of FAA and nanoparticles to take advantage of RBE, the present work consists of synthesizing mesoporous silica nanoparticles followed by its functionalization with AFF, a GJ blocker, and its efficacy in protecting normal cells from EBR after being exposed to gamma radiation (50Gy). Characterizations were done in order to determine morphological and structural features of the MSN synthesized as well as the presence of organic components after the functionalization process. The synthesis of MCM-41 was successful which its hexagonal pore arrangement was maintained even after the functionalization steps with APTES and FFA. All the samples tested in fibroblast MRC-5 and cell of tumoral lineage, HeLa, showed that materials were highly compatible and of very low cytotoxicity. The response of human fibroblasts, MRC-5, to EBR was also determined. HeLa cells were exposed to 50 Gy of gamma ray radiation in the presence of all materials and the culture media was, then, transferred to MRC-5A Live/Dead assay was carried out to determine the radiation bystander effects in fibroblast MRC-5. Only the culture media of HeLa cells treated with MCM-41/AP-2xAFF and MCM-41/0,5AP–AFF before exposure to gamma-radiation were able to avoid apoptosis of MRC-5 cells that received the irradiated media, suggesting that the FFA was the protector agent. The results obtained showed the potential of MCM-41 grafted with FFA as a protector of normal cells from radiation bystander effects triggered by signaling molecules of irradiated cells during radiotherapy. (author)