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.

Nanoparticle (NP) assisted magnetic hyperthermia (NMH) is a clinically proven method for cancer treatment. High-Z magnetic NPs could also be a perspective object for combining hyperthermia with tumor radiosensitization. However, this application of NPs is little studied, and it is unclear as to what particle compositions one can rely on. Therefore, the present work focuses on the search of materials that combine alternating magnetic field induced heating and high atomic number related dose enhancement abilities. A theoretical evaluation of 24 promising NP compositions was performed: the values of dose enhancement factor (DEF) were determined for kilovoltage x-ray spectra (30–300 kVp), as well as specific absorption rate (SAR) values were calculated for various combinations of elemental compositions and particle size distributions. For the alternating magnetic fields with amplitude 75–200Oe and frequency 100kHz, the maximum obtained SAR values ranged from 0.35 to 6000Wg−1, while DEF values for studied compounds ranged from 1.07 to 1.59. The increase in the monodispersity of NPs led to a higher SAR, confirming well-known experimental data. The four types of SAR dependences on external magnetic field amplitude and anisotropy constant were found for various particle sizes. The most predictable SAR behavior corresponds to larger NPs (∼70–100 nm). Thus, based on these calculations, the most promising for the combination of NMH with radiotherapy, from a physical point of view, are La0.75Sr0.25MnO3, Gd5Si4, SmCo5, and Fe50Rh50. The greatest dose enhancement is expected for superficial radiotherapy (in the voltage range up to ∼60 kVp).

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The development of the physicochemical basis for applications of nanoradiosensitizers for targeted treatment of tumors is one of the crucial issues of modern radiotherapy. Ceramic nanoparticles (NPs) composed of heavy metal oxides are considered as prospective sensitizers, particularly for X-ray treatment. This study reports a novel approach for experimental simulations of the radiosensitizing effect of NPs in biomimetic systems based on the quantification of radicals produced from organic components in concentrated aqueous organic solutions using the spin-trapping technique with electron paramagnetic resonance detection. This approach was first applied to X-ray irradiation (45 kVp) of aqueous methanol solutions systems containing different concentrations of hafnium oxide nanoparticles with an average diameter of ca. 84 nm (up to 1.8 wp). It was found that the amount of radicals produced from methanol at the same exposition time increased linearly with the increasing content of HfO 2 NPs. The effect can be reasonably explained by the physical enhancement mechanism associated with efficient transfer of absorbed energy from the NPs to aqueous organic medium. The Monte Carlo simulations were applied to calculate the absorbed dose in the studied systems as a function of NP concentration. The experimental enhancement factor in the formation of radicals (0.71 wp −1 ) was found to be slightly lower than the calculated coefficient of the absorbed dose enhancement (0.80 wp −1 ), which can be explained by partial self-absorption of generated secondary electrons inside rather bulky HfO 2 nanoparticles. The proposed model approach may provide a rational ground for comparative studies of different nanoradiosensitizers and the optimization of the NP size, photon energy, and other factors.