Optimal scheduling of the nanoparticle-mediated cancer photo-thermo-radiotherapy

Maximal synergistic effect between photothermal therapy and radiotherapy (RT) may be achieved when the interval between these two modalities is optimal. In this study, we tried to determine the optimal schedule of the combined regime of RT and nano-photothermal therapy (NPTT), based on the cell cycle distribution and kinetics of cell death. To this end, alginate-coated iron oxide-gold core-shell nanoparticles (Fe3O4@Au/Alg NPs) were synthesized, characterized, and their photo-radio sensitization potency was evaluated on human nasopharyngeal cancer KB cells. Our results demonstrated that synthesized NPs have a good potential in radiotherapy and near-infrared (NIR) photothermal therapy. However, results from flow cytometry analysis indicated that a major portion of KB cells were accumulated in the most radiosensitive phases of cell cycle (G2/M) 24 h after NPTT. Moreover, the maximal synergistic anticancer efficacy (12.3 cell viability) was observed when RT was applied 24 h following the administration of NPTT (NPs 30 μg/mL, 4 h incubation time + Laser 808 nm, 1 W/cm2, 5 min + RT 6 Gy). It is noteworthy that apoptosis was the dominant cell death pathway in the group of cells treated by combination of NPTT and RT. This highly synergistic anticancer efficacy provides a mechanistic basis for Fe3O4@Au/Alg NPs-mediated photothermal therapy combined with RT. Knowing such a basis is helpful to promote novel nanotechnology cancer treatment strategies. © 2020 Elsevier B.V

Knocking down the DRD2 by shRNA expressing plasmids in the nucleus accumbens prevented the disrupting effect of apomorphine on prepulse inhibition in rat

Prepulse Inhibition (PPI), the objective measure of sensorimotor gating disturbance has being widely used in animal models of schizophrenia. Dopaminergic direct and indirect agonists impair PPI. However, the profile of dopaminergic receptors involved in PPI impairment by dopamine agonists is not clear. By injecting shRNA expressing plasmids against dopamine D2 receptor genes (DRD2) in the nucleus accumbens, here, we studied the effect of apomorphine on PPI in D2 down-regulated rats. Seventy two adult Wistar rats assigned randomly in nine groups, each received coding (250 and 500 ng/μl) or noncoding shRNA expressing plasmids against DRD2 in the nucleus accumbens, with or without apomorphine (0.5 mg/kg, S.C., 72 hours after treatment with plasmids). Auditory startle response and PPI were measured after apomorphine injection. Real time RT-PCR was used to measure DRD2 expression. Results showed that apomorphine significantly decreased PPI in noncoding plasmid treated rats; While, PPI did not impaired in rats pretreated with 250 and 500 ng/μl shRNA expressing plasmids. Accordingly, the expression of DRD2 mRNA in the nucleus accumbens showed 72-78 decrease in expressing plasmid treated rats. Additionally, treatment with expressing plasmids had no effect on basal PPI and/or auditory startle response. Taken together, our results demonstrated that DRD2 silencing in the nucleus accumbens can prevent PPI impairment by apomorphine. These observations suggest application of molecular techniques such as the use of shRNA against DRD2s in studies of schizophrenia pathophysiology and development of new treatments in schizophrenia

Effects of proton irradiation on flux-pinning properties of underdoped Ba(Fe0.96Co0.04)(2)As-2 pnictide superconductor

We study the effect of proton irradiation on Ba(Fe0.96Co0.04)2As2 superconducting single crystals from combined magnetisation and magnetoresistivity measurements. The study allows the extraction of the values of the apparent pinning energy U0 of the samples prior to and after irradiation, as well as comparison of the values of U0 obtained from the flux-flow reversible region with those from the flux-creep irreversible region. Irradiation reduces Tc modestly, but significantly reduces U0 in both regimes: the critical current density Jc is modified, most strikingly by the disappearance of the second magnetisation peak after irradiation. Analysis of the functional form of the pinning force and of the temperature dependence of Jc for zero field, indicates that proton irradiation in this case has not changed the pinning regime, but has introduced a high density of shallow point-like defects. By considering a model that takes into account the effect of disorder on the irreversibility line, the data suggests that irradiation produced a considerable reduction in the average effective disorder overall, consistent with the changes observed in U0 and Jc