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.

Recently, the combined therapy has become one of the main approaches in cancer treatment. Combining different approaches may provide a significant outcome by triggering several death mechanisms or causing increased damage of tumor cells without hurting healthy ones. The supramolecular nanoplatform based on a high-Z metal reported here is a suitable system for the targeted delivery of chemotherapeutic compounds, imaging, and an enhanced radiotherapy outcome. HfO2 nanoparticles coated with oleic acid and a monomethoxypoly­(ethylene glycol)-poly­(ε-caprolactone) copolymer shell (nanoplatform) are able to accumulate inside cancer cells and release doxorubicin (DOX) under specific conditions. Neither uncoated nor coated nanoparticles show any cytotoxicity in vitro. DOX loaded onto a nanoplatform demonstrates a lower IC50 value than pure DOX. X-ray irradiation of cancer cells loaded with a nanoplatform shows a higher death rate than that for cells without nanoparticles. These results provide an important foundation for the development of complex nanoscale systems for combined cancer treatment.