Gold nanoparticles (GNPs) emerged as promising antitumor radiosensitizers. However, the complex dependence of GNPs radiosensitization on the irradiation conditions remains unclear. In the present study, we investigated the impacts of the dose rate and photon energy on damage of the pBR322 plasmid DNA exposed to X-rays in the presence of 12 nm, 15 nm, 21 nm, and 26 nm GNPs. The greatest radiosensitization was observed for 26 nm GNPs. The sensitizer enhancement ratio (SER) 2.74 ± 0.61 was observed at 200 kVp with 2.4 mg/mL GNPs. Reduction of X-ray tube voltage to 150 and 100 kVp led to a smaller effect. We demonstrate for the first time that the change of the dose rate differentially influences on radiosensitization by GNPs of various sizes. For 12 nm, an increase in the dose rate from 0.2 to 2.1 Gy/min led to a ~1.13-fold increase in radiosensitization. No differences in the effect of 15 nm GNPs was found within the 0.85–2.1 Gy/min range. For 21 nm and 26 nm GNPs, an enhanced radiosensitization was observed along with the decreased dose rate from 2.1 to 0.2 Gy/min. Thus, GNPs are an effective tool for increasing the efficacy of orthovoltage X-ray exposure. However, careful selection of irradiation conditions is a key prerequisite for optimal radiosensitization efficacy.

This article discusses the design and analysis of a new chemical chemosensor for detecting mercury(II) ions. The chemosensor is a hydrazone made from 4-methylthiazole-5-carbaldehyde and fluorescein hydrazide. The structure of the chemosensor was confirmed using various methods, including nuclear magnetic resonance spectroscopy, infrared spectroscopy with Fourier transformation, mass spectroscopy, and quantum chemical calculations. The sensor’s ability in the highly selective and sensitive discovery of Hg²⁺ ions in water was demonstrated. The detection limit for mercury(II) ions was determined to be 0.23 µM. The new chemosensor was also used to detect Hg²⁺ ions in real samples and living cells using fluorescence spectroscopy. Chemosensor 1 and its complex with Hg²⁺ demonstrate a significant tendency to enter and accumulate in cells even at very low concentrations.

Nanoparticles (NPs) with a high atomic number (Z) are promising radiosensitizers for cancer therapy. However, the dependence of their efficacy on irradiation conditions is still unclear. In the present work, 11 different metal and metal oxide NPs (from Cu (Z_Cu = 29) to Bi₂O₃ (Z_Bi = 83)) were studied in terms of their ability to enhance the absorbed dose in combination with 237 X-ray spectra generated at a 30–300 kVp voltage using various filtration systems and anode materials. Among the studied high-Z NP materials, gold was the absolute leader by a dose enhancement factor (DEF; up to 2.51), while HfO₂ and Ta₂O₅ were the most versatile because of the largest high-DEF region in coordinates U (voltage) and E_eff (effective energy). Several impacts of the X-ray spectral composition have been noted, as follows: (1) there are radiation sources that correspond to extremely low DEFs for all of the studied NPs, (2) NPs with a lower Z in some cases can equal or overcome by the DEF value the high-Z NPs, and (3) the change in the X-ray spectrum caused by a beam passing through the matter can significantly affect the DEF. All of these findings indicate the important role of carefully planning radiation exposure in the presence of high-Z NPs.

Olivomycin A (OA), an antibiotic of the aureolic acid family, interferes with gene transcription upon forming complexes with GC-rich regions in the DNA minor groove. We demonstrate that the mechanism of transcriptional deregulation is not limited to OA interaction with GC-containing binding sites for transcription factors. Using electrophoretic mobility shift assays and DNAse I footprinting of cytomegalovirus (CMV) promoter fragments carrying OA-preferred GC tetrads (CMVwt), we showed OA binding specifically to GC islands. Replacement of G for A in these tetrads (CMVmut) abrogated OA binding. Furthermore, OA decreased RNA polymerase II (RNAPII) binding to the CMVwt promoter and inhibited the reporter gene expression. In line with the absence of OA binding sites in CMVmut DNA, the expression driven from this promoter was weakly sensitive to OA. In the endogenous genes OA decreased RNAPII on promoters and coding regions. In certain cases this phenomenon was concomitant with the increased histone 3 abundance. However, the sensitivity to OA did not correlate with GC patterns around transcription start sites, suggesting that certain GC stretches play unequal roles in OA-induced transcriptional perturbations. Thus, OA affects transcription via complex mechanisms in which GC tetranucleotide binding causes RNAPII/chromatin alterations differentially manifested in individual gene contexts.

GC-rich stretches in the DNA minor groove are the established intracellular targets for the aureolic acid group of antibiotics such as olivomycin A and its semisynthetic analogue olivamide. We demonstrated here that both antibiotics at nanomolar concentrations inhibited transcription of the c-Myc oncogene in cultured human tumor cells. The mechanism of transcriptional inhibition did not require the full-length binding site for Sp1, a GC-dependent transcriptional factor. GC quartets with the nucleotide sequences optimal for drug binding are sufficient for c-Myc transcriptional block by the aureolic acid derivatives.