Modulation of cancer cells' radiation response in the presence of folate conjugated Au@Fe2O3 nanocomplex as a targeted radiosensitizer.

OBJECTIVES: To investigate the effects of Au@Fe2O3 core-shell nanoparticle (NP), with and without conjugation to folic acid (FA) as a targeting ligand, on radiosensitization of both cancer and healthy cells. METHODS: Au@Fe2O3 NPs were first synthesized, then modified with FA, and finally characterized. Radiation dose enhancement studies were performed on KB cancer cells and L929 healthy cells. NPs at the concentration of 20 µg/ml were first incubated with both cell lines and then different doses of 6 MV X-ray radiation were examined. The end effects were evaluated via MTT assay and flow cytometry using AnnexinV/PI kit. RESULTS: It was indicated that viability of KB cells has a much lower rate than L929 cells when the cells were treated by {(FA-Au@Fe2O3) + (X-ray)} regimen. Cell viability was even decreased significantly when X-ray dose increased. Moreover, flow cytometry studies revealed that FA-targeted NPs induced higher level of apoptosis for KB cancer cells than L929 healthy cells. CONCLUSION: Our findings provide a new perspective on high ability of the synthesized FA-targeted Au@Fe2O3 NPs which may be considered as an efficient radiosensitizer in the process of targeted radiation therapy of cancer.

Radiosensitizer effect of usnic acid on Biomphalaria glabrata embryos.

PURPOSE: Some phytochemicals have shown the potential of being radiomodifiers, especially phenolic compounds, such as lichenic secondary metabolites. To evaluate the phytochemical usnic acid as a radiomodifier, embryonic cells of molluscs have been used due to their ease of collection, high sensitivity to physical and chemical agents, well-known embryology and low cost for analysis. MATERIALS AND METHODS: This study aimed to assess the radiosensitizing action of usnic acid on Biomphalaria glabrata embryos. Samples were irradiated with 4 Gy of gamma rays from a 60Co source (dose rate 2.906 Gy/h). An acute toxicity test was performed using B. glabrata embryos in the blastula stage, in order to determine the toxicity of usnic acid and to establish the lethal Concentration for 50% (LC50). Subsequently, the radiomodifing capacity of usnic acid was estimated using assays with B. glabrata embryos. RESULTS: Irradiation increased the number of non-viable embryos compared to unirradiated controls. Additionally, it was observed that embryos exposed to a non-toxic concentration of usnic acid (0.6 µg/mL) before irradiation showed a further enhancement in non-viable embryos when compared with exposure to ionizing radiation alone. CONCLUSION: The results presented here indicate that usnic acid makes cells more sensitive to the damaging effects of radiation.

Radiosensitization by gold nanoparticles.

Recent years brought increasing use of gold nano particles (GNP) as a model platform for interaction of irradiation and GNPs aiming radiosensitization. Endocytosis seems to be one of the major pathways for cellular uptake of GNPs. Internalization mechanism of GNPs is likely receptor-mediated endocytosis, influenced by GNP size, shape, its coating and surface charging. Many showed that DNA damage can occur as a consequence of metal-enhanced production of low energy electrons, Auger electrons and alike. Kilovoltage radiotherapy (RT) carries significantly higher dose enhancement factor (DEF) that is observed with megavoltage irradiations, the latter usually been at the order of 1.1-1.2. Higher gold concentrations seem to carry higher risk of toxicity, while with lower concentrations the DEF can be reduced. Adding a chemotherapeutic agent could increase level of enhancement. Clinical trials are eagerly awaited with a promise of gaining more knowledge deemed necessary for more successful transition to widespread clinical practice.

Taxanes: the genetic toxicity of paclitaxel and docetaxel in somatic cells of Drosophila melanogaster.

In this study, the taxanes, paclitaxel and docetaxel were investigated for genotoxicity in the wing spot test of Drosophila melanogaster. These relatively new drugs are used in cancer therapy and show great promise in the treatment of a variety of cancers. Their major cellular target is the alpha,beta-tubulin dimer but, unlike other spindle poisons, they stabilize microtubules by a shift towards assembly, producing nonfunctional microtubule bundles. The Drosophila wing Somatic Mutation and Recombination Test (SMART) provides a rapid means to evaluate agents able to induce gene mutations and chromosome aberrations, as well as rearrangements related to mitotic recombination. We applied the standard version of SMART (with normal bioactivation) and a variant version with increased cytochrome P450-dependent biotransformation capacity. In the standard assay, docetaxel was found to be aneuploidogenic; this was effectively abolished by a high cytochrome P450-dependent detoxification capacity. This suggests, as previously reported, the involvement of this family of enzymes in the detoxification of docetaxel rather than in its activation. In contrast, paclitaxel was clearly non-genotoxic at the same (millimolar) concentrations as used for docetaxel in both crosses. The weak responsiveness of SMART assays to aneugenic compounds, the weaker ligand and assembly action of paclitaxel and the more rapid reversibility of the microtubules formed with this compound, may have caused the negative response observed in the present study.