Combined X-ray radiotherapy and laser photothermal therapy of melanoma cancer cells using dual-sensitization of platinum nanoparticles.

Metal nanostructures are promising agents sensitizing by laser light and X-ray in photothermal therapy (PTT) and radiotherapy (RT) of cancer that improve treatment strategies of cancer. Nanoscale platinum materials are favorable in nanomedicine applications. In this study, platinum nanoparticles (PtNPs) were synthesized and applied for cancer therapy upon 808-nm laser light and X-ray radiation, or their combination. Two power densities of laser (1.0 and 1.5 W cm-2) and three X-ray doses (2, 4 and 6 Gy) were selected for irradiation of B16/F10 cell line at 24 and 72 h-post treatment. The synthesized PtNPs had a spherical shape with a diameter of 12.2 ± 0.7 nm, and were cytocompatible up to 250 µg mL-1. A photothermal conversion activity in a concentration-dependent manner at 72 h-post treatment was observed. Also, PtNPs represented cytotoxicity upon X-ray radiation doses of 2, 4, and 6 Gy after 24 h, while, 72-h time passing led to deeper outcomes. Dual radiation of laser light and X-ray into PtNPs considerably improved the treatment via reactive oxygen species (ROS) production. PtNPs can act as a novel dual absorber of laser light and X-ray, a common sensitizer, for treatment of cancer. The results of this study can be considered after further clinical investigations for treatment of tumor models.

Enhanced melanoma cell-killing by combined phototherapy/radiotherapy using a mesoporous platinum nanostructure.

BACKGROUND: Metal nanomaterials have a significant potential as photosensitizer and radiosensitizer. The purpose of this study was to evaluate the cytotoxicity of a platinum mesoporous nanostructure (Pt MN) toward a melanoma cancer cell line upon combined laser radiation (808 nm, 1 and 1.5 W cm-2) and X-ray irradiation (6 MV, 2, 4, and 6 Gy). METHODS: Pt MN was synthesized by a simple procedure and characterized by field emission scanning and transmission electron microscopy. A mouse malignant melanoma cell line C540 (B16/F10) was treated with Pt MN, laser light and/or X-ray. RESULTS: Pt MN had a mesoporous structure with a sponge-resemble shape comprised of ensembles of very small adhered particles of <11 nm and about 5-nm pores. While Pt MN represented a low toxicity toward and considerable uptake into the cell line in a concentration range of 10-100 µg mL-1, laser light radiation alone was also not toxic, and X-ray irradiation alone induced a limited toxicity, Pt MN was toxic against the cells in a dose dependent manner upon laser light radiation, X-ray irradiation, or their combined exposure. The killing efficacy of Pt MN upon X-ray irradiation was more obvious at 72 h post-treatment. The combined exposure (laser radiation followed by X-ray irradiation) led to a deep cell killing and a very low melanoma cell viability (∼1%). Significant melanoma cancer cell killing of Pt MN was due to reactive oxygen species (ROS) production upon combined exposure of laser and X-ray, while cell killing upon laser light radiation was due to heat generation. CONCLUSION: Pt MN was introduced as a supreme laser/X-ray sensitizer for treatment of cancer with a high ability to produce ROS and a potent impact on decreasing cell viability.

Sonodynamic cancer therapy by a nickel ferrite/carbon nanocomposite on melanoma tumor: In vitro and in vivo studies.

Reactive oxygen species (ROS)-mediated cancer therapy using light or ultrasound (US) has been widely approached as a non-invasive and inspiring alternative treatment. Sonodynamic therapy (SDT), a non-invasive therapeutic modality of cancer, is an outcome of low-intensity US effect on cancer cells using a sonosensitizer, which results in heat and ROS production followed by cell death. The aim of this study was synthesis, characterization and cancer SDT application of a nickel ferrite/carbon nanocomposite (NiFe2O4/C), as a sonosensitizer. SDT was carried out by applying a 1.0-MHz US radiation at 1.0 W cm-2 of power density and 100% pulse ratio for 60 s. A significant C540 (B16/F10) cell killing was observed in vitro due to ROS production of 100 µg mL-1 of NiFe2O4/C upon SDT. In addition, SDT of melanoma cancer in a mouse model using intratumorally injected NiFe2O4/C of 100 µg mL-1 produced remarkable efficacious recovery in the tumor and significant necrosis (up to 60%) in histological assessments, while injection of NiFe2O4/C or US irradiation alone induced no healing effect. Therefore, SDT using NiFe2O4/C attained success in destroying melanoma cancer and can be developed and introduced as an alternative treatment strategy for melanoma cancer. In furtherance of SDT, magnetic resonance (MR) imaging (1.5 T) in an agarose phantom indicated the effectiveness of NiFe2O4/C as a negative contrast agent in transverse relaxation time-weighted imaging with a corresponding relaxation rate (r2) of 78.9 mmol L-1 s-1. The results confirmed the applicability of the nanocomposite as a theranostics agent for simultaneous SDT and MR imaging.

Down-regulation of CatSper 1 and CatSper 2 genes by lead and mercury.

In the study of the expression of CatSper genes, consideration of the effects of environmental metal toxicity is very important. Therefore, in this study, the effects of lead acetate and mercury chloride exposure on expression of CatSper genes, sperm parameters, histology of testis and prooxidant antioxidant balance (PAB) values of serum were investigated. A total of 28 mice was divided into four groups. The control group did not receive injections. The sham group received normal saline intraperitoneally. Lead and mercury groups were injected 60 and 1.25 mg/kg/daily lead acetate and mercury chloride respectively intraperitoneally for 2 weeks. After 35 days, the sperm analysis and histology of left testis were performed. In addition, serum was obtained to measure the PAB values. The right testis was used for molecular analysis of real-time PCR. Administration with either lead acetate or mercury caused significant damage to the seminiferous tubules as well as a reduction in sperm parameters compared to the control group. The relative expression of CatSper 1 and CatSper 2 in the lead group was lower than that of the control group (-0.01 ±â€¯0.24, -0.007 ±â€¯0.52 vs. 1 ±â€¯0.50, P = 0.34). The relative expression of CatSper 1 and CatSper 2 was significantly lower in the mercury group compared to the control ones (-0.24 ±â€¯2.28, -4.49 ±â€¯4.86 vs. 1 ±â€¯0.50, P = 0.21). PAB values significantly increased in lead or mercury exposed- mice compared to the control ones (0.93 ±â€¯0.17, 1.54 ±â€¯0.17 vs. 0.51 ±â€¯0.11; P ≤ 0.000). The results of this study showed that administration with either lead acetate or mercury chloride caused degenerative damage in seminiferous tubules and reduction in sperm quality and expression of CatSper 1, 2 genes in mice. Therefore, it is possible in infertile men who have had exposure to lead acetate or mercury chloride. Owing to structural similarities, these metals are substitutes for calcium ions and have effects on calcium channels. These cause immobility in sperm by blocking CatSper-specific calcium channels. However, more studies are required to elucidate the mechanism underlying the impact of different doses of heavy metals on CatSper genes expression.

Master file size and apical transportation in severely curved root canals.

OBJECTIVES: A curvature leads to asymmetrical removal of root dentine, which results in an increase in the incidence of canal transportation. The aim of this study was to evaluate the effect of master apical file (MAF) size on the apical transportation (AT) of teeth with severe canal curvatures. METHODS: Thirty-six mesial roots of human mandibular first molars were included. Inclusion criteria consisted of mature roots with closed apices, absence of carious lesions and resorptions, and root canal curvatures (CC) of 45 degrees < CC < 60 degrees. The root canals were prepared using a crown-down pressureless technique. The samples were equally divided into groups A, B, and C based on MAF size: group A: MAF size equivalent to #20; group B: MAF size equivalent to #25, and group C: MAF size equivalent to #30. Cone beam computed tomography was used to evaluate the AT. RESULTS: There were no statistically significant differences in the AT between the canals with different curvature angles up to MAF size #30 (P = 0.55). CONCLUSION: Using flexible hand files for canal preparation, an increase in MAF size up to #30 does not significantly influence AT in severely curved canals.