pH-Activatable tumor-targeting gold nanoprobe for near-infrared fluorescence/CT dual-modal imaging in vivo.

One hallmark of solid tumors, regardless of its type or stage, is the existence of an unsual acidic microenvironment, which has been considered a specific and ideal target for cancer imaging. Therefore, we developed a pH-activatable nanoprobe GNPs-CKL-FA for near-infrared fluorescence (NIR) and computed tomography (CT) imaging of tumors. This nanoprobe consists of a near-infrared fluorophore (Cy5.5), a pH-sensitive ketal linker, and gold nanoparticles (GNPs) decorated with folates that could bind to tumor cells' surface receptors to promote cellular internalization. This ability of folate to mediate tumor targeting and accelerate internalization has been confirmed by in vitro experiments with HeLa cells. The fluorescence of the nanoprobes successfully activated by low intracellular pH, especially in more acidic organelles. Furthermore, fluorescence signals increased to a greater extent when the pH in tumors was lowered by injection of acetate buffer and isoproterenol. The CT contrast of GNPs-CKL-FA was obtained after administering intravenously to HeLa subcutaneous tumor-bearing mice. These results suggest that GNPs-CKL-FA has the potential to be a pH-activatable fluorescent nanoprobe combined with CT contrast agent for tumor targeted imaging.

Diaphragm contractile dysfunction causes by off-target low-dose irradiation.

BACKGROUND: Diaphragm is a primary inspiratory muscle and often receives off-target dose in patients with thoracic radiotherapy, and whether acute effect of low dose irradiation would cause contractile dysfunction of the diaphragm remains unclear. We use a rat model to investigate the effect of low-dose irradiation on diaphragm contractile function in the current study. METHODS: The radiation dose distributions in patients with esophageal cancer receiving radiotherapy were calculated to determine the dose received by the off-target diaphragm area. Rats were randomly assigned to an irradiated or a non-irradiated control group (n = 10 per group). A single-fraction of 5 Gy radiation was then delivered to the diaphragms of Sprague-Dawley rats in the irradiated group. The control group received sham irradiation (0 Gy). Rats were sacrificed 24 hours after the irradiation procedures and diaphragms were removed en bloc for contractile function assessment, oxidative injury and DNA damage analysis. Oxidative injury was determined by analyzing concentration of protein carbonyls and DNA damage was determined by analyzing retention of γH2AX foci in nuclei of diaphragmatic tissue. RESULTS: At 24 hours after delivery of a single dose of 5 Gy radiation, specific twitch (p = 0.03) and tetanus tension (p = 0.02) were significantly lower in the irradiated group than in the control group. The relative force-frequency curves showed a significant downward shift in the irradiated group. Protein carbonyl level (p < 0.01) and percentage of γH2AX-positive diaphragm muscle cells were significantly higher in the irradiated group than in the control group 24 hours after irradiation (58% vs. 30%, p = 0.01). CONCLUSIONS: Off-target low dose irradiation could induce acute contractile dysfunction of the diaphragm which was related to radiation-induced direct DNA and indirect oxidative damage.