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Radiotherapy is one of the most efficient methods of cancer treatment, and sometimes it is the only effective option. The combination of this approach with radiosensitizers was proposed to both increase the radiotherapy efficiency and reduce the unwanted effects of radiation on healthy tissues. Over the past few years nanoparticles containing elements with a high atomic number (relative to soft biological tissues) in the form of metals or metal oxide has been attracted attention as radiosensitizers. The effect of nanosensitizers is generally based on radiation physics and radiation chemistry related to the peculiarities of energy absorption and subsequent reactions of radicals in organized systems. The purpose of this work is to probe the role of different enhancement mechanisms in the X-ray irradiated oxygen-free model aqueous organic systems containing stabilized metal oxide nanoparticles. Metal oxide nanoparticles (HfO2, CeO2, and WO3) were synthesized using the approaches of sol-gel synthesis and hydrothermal synthesis. Basic features of our experimental approach for spin trapping technique with EPR detection of radiation-induces adducts with the selected spin trap (C-phenyl-N-tert-butylnitrone, PBN) were described previously [1, 2]. The main idea is that the OH• radicals mainly produced in the system NPs/methanol/PBN/water quantitatively react withmethanol to yield CH2OH• radicals, which form stable and easily measurable adducts CH2OH•-PBN. The ratio between absorbed dose in the Fricke dosimeter and in the irradiated samples was determined by the Monte Carlo simulation using the Geant4 program code. The results obtained in our study show that the sensitizing effect of metal oxide nanoparticles in the X-ray irradiated oxygen-free aqueous organic systems could be attributed to the increasing absorbed dose due to high absorption cross-section of “heavy” metal atoms known as physical enhancement. The comparison with calculations shows that using relatively small NPs probably provides the maximum value, which can be obtained for the corresponding NPs in each case (as judged by the calculations). The effects related to the so-called chemical enhancement are noticeable only for the oxygen-containing systems and were not observed in our experiments. In practical sense, these results urge the development of new efficient approaches for the radiation treatment of hypoxic media using nanoparticles.