The development of potentially safe radiosensitizing agents is essential to enhance the treatment outcomes of radioresistant cancers. The titanium peroxide nanoparticle (TiOxNP) was originally produced using the titanium dioxide nanoparticle, and it showed excellent reactive oxygen species (ROS) generation in response to ionizing radiation. Surface coating the TiOxNPs with polyacrylic acid (PAA) showed low toxicity to the living body and excellent radiosensitizing effect on cancer cells. Herein, we evaluated the mechanism of radiosensitization by PAA-TiOxNPs in comparison with gold nanoparticles (AuNPs) which represent high-atomic-number nanoparticles that show a radiosensitizing effect through the emission of secondary electrons. The anticancer effects of both nanoparticles were compared by induction of apoptosis, colony-forming assay, and the inhibition of tumor growth. PAA-TiOxNPs showed a significantly more radiosensitizing effect than that of AuNPs. A comparison of the types and amounts of ROS generated showed that hydrogen peroxide generation by PAA-TiOxNPs was the major factor that contributed to the nanoparticle radiosensitization. Importantly, PAA-TiOxNPs were generally nontoxic to healthy mice and caused no histological abnormalities in the liver, kidney, lung, and heart tissues.

The precise mechanism of intercellular communication between cancer cells following radiation exposure is unclear. Exosomes are membrane-enclosed small vesicles comprising lipid bilayers and are mediators of intercellular communication that transport a variety of intracellular components, including microRNAs (miRNAs or miRs). The present study aimed to identify novel roles of exosomes released from irradiated cells to neighboring cancer cells. In order to confirm the presence of exosomes in the human pancreatic cancer cell line MIAPaCa-2, ultracentrifugation was performed followed by transmission electron microscopy and nanoparticle tracking analysis (NanoSight) using the exosome-specific surface markers CD9 and CD63. Subsequent endocytosis of exosomes was confirmed by fluorescent microscopy. Cell survival following irradiation and the addition of exosomes was evaluated by colony forming assay. Expression levels of miRNAs in exosomes were then quantified by microarray analysis, while protein expression levels of Cu/Zn- and Mn-superoxide dismutase (SOD1 and 2, respectively) enzymes in MIAPaCa-2 cells were evaluated by western blotting. Results showed that the uptake of irradiated exosomes was significantly higher than that of non-irradiated exosomes. Notably, irradiated exosomes induced higher intracellular levels of reactive oxygen species (ROS) and a higher frequency of DNA damage in MIAPaCa-2 cells, as determined by fluorescent microscopy and immunocytochemistry, respectively. Moreover, six up- and five downregulated miRNAs were identified in 5 and 8 Gy-irradiated cells using miRNA microarray analyses. Further analysis using miRNA mimics and reverse transcription-quantitative PCR identified miR-6823-5p as a potential candidate to inhibit SOD1, leading to increased intracellular ROS levels and DNA damage. To the best of our knowledge, the present study is the first to demonstrate that irradiated exosomes enhance the radiation effect via increasing intracellular ROS levels in cancer cells. This contributes to improved understanding of the bystander effect of neighboring cancer cells.

Investigation of the potential of using TiO2 nanoparticles as a contrast agent in computed tomography and magnetic resonance imaging

Aim: CyberKnife is the most advanced form of stereotactic body radiotherapy (SBRT) system that uses a robotic arm to deliver highly focused beams of radiation; however, a limitation is that it only irradiates from ceiling to floor direction. In patients with posterior lungs tumour who are positioned supine, normal lung tissue may suffer undesirable radiation injuries. This study compares the treatment planning between the prone set-up and the supine set-up for lung cancer in CyberKnife SBRT to decrease normal lung dose to avoid radiation side effects. Materials and methods: A human phantom was used to generate 108 plans (54 for prone and 54 for supine) using the CyberKnife planning platform. The supine and prone plans were compared in terms of the dosimetric characteristics, delivery efficiency and plan efficiency. Results: For posterior targets, the area of low-dose exposure to normal lungs was smaller in the prone set-up than in the supine set-up. V10 of the lungs was 7·53% and 10·47% (p < 0·001) in the anterior region, and 10·78% and 8·03% (p < 0·001) in the posterior region in the supine and prone set-up plans, respectively. Conclusions: The comparison between the prone set-up and the supine set-up was investigated with regard to target coverage and dose to organs at risk. Our results may be deployed in CyberKnife treatment planning to monitor normal tissue dose by considering patient positioning. This may assist in the design of better treatment plans and prevention of symptomatic radiation pneumonitis in lung cancer patients.

Gastrointestinal toxicity is frequently observed secondary to accidental or therapeutic radiation exposure. However, the variation in the intestinal metabolites after abdominal radiation exposure remains ambiguous. In the present study, C57BL/6 mice were exposed to 0, 2, and 20 Gy irradiation dose. The Head and chest of each mouse were covered with a lead shield before x-ray irradiation. 24 h post-irradiation treatment, intestinal tissue of each mouse was excised and prepared for metabolites measurement using gas chromatography-mass spectrometry (GC-MS). Our comprehensive analysis of metabolites in the intestinal tissues detected 44 metabolites after irradiation, including amino acids, carbohydrates, organic acids, and sugars. Amino acid levels in the intestinal tissue gradually rose, dependent on the radiation dose, perhaps as an indication of oxidative stress. Our findings raise the possibility that amino acid metabolism may be a potential target for the development of treatments to alleviate or mitigate the harmful effects of oxidative stress-related gastrointestinal toxicity due to radiation exposure.