Defense of the dissertation of Kaliekperova Kamila Bakhtzhankyzy for the degree of Doctor of Philosophy (PhD) in the educational program «8D07140 - Nanomaterials and nanotechnologies»
The defense of the dissertation for the degree of Doctor of Philosophy (PhD) by Kaliyekperova Kamila on the topic «Study of the effect of variations in the phase composition of iron-containing nanocomposites on their hyperthermic properties and cytotoxicity» according to the educational program «8D07140 – Nanomaterials and nanotechnologies» will be held at the L.N. Gumilyov Eurasian National University.
The dissertation was carried out at the «Nuclear physics, new materials and technologies education department» of L.N. Gumilyov Eurasian National University.
The language of defense is russian
Official reviewers:
- Satbayeva Zarina Askarbekovna – PhD, professor-researcher of «Technical Physics and Heat Power Engineering» department, Shakarim University (Semey, Republic of Kazakhstan);
- Kenzhina Laura Bolatkazyevna – Candidate of Medical Sciences, Associate Professor, Head of the Laboratory of Biodosimetric Research of the Department of Radioecological and Biodosimetric Research of the IRSE branch of the RSE NNC RK.
Temporary members of the Dissertation Council:
- Yerlanuly Yerassyl – PhD, Head of the Centre Environmental Engineering, Kazakh-British Technical University (Almaty, Republic of Kazakhstan);
- Aidarova Saule Baylyarovna – Doctor of Chemical Sciences, professor of the Kazakh-British Technical University (Almaty, Kazakhstan);
- Maksym Buryi – PhD, Head of Plasma Chemical Technologies Department, Institute of Plasma Physics of the CAS (Prague, Czech Republic).
Scientific advisors:
Kozlovskiy Artem Leonidovich – PhD, Associate Professor, Department of Nuclear Physics, New Materials and Technologies, L.N. Gumilyov Eurasian National University (Astana, Republic of Kazakhstan)
Tishkevich Darya Ivanovna – Candidate of Physical and Mathematical Sciences, Leading Researcher of the State Association «Scientific and Practical Center of the National Academy of Sciences of Belarus for Materials Science» (Minsk, Republic of Belarus)
The defense will take place on June 08, 2026, at 04:00 PM in the Dissertation Council for the training direction «8D071 – Engineering and engineering trades» in the specialty «8D07140 – Nanomaterials and nanotechnologies» of L.N. Gumilyov Eurasian National University. The dissertation council meeting will be held in a mixed (offline and online) format.
Link: https://clck.ru/3TS9Ug
Address: Astana, Kazhymukan Street 13, Room 309.
Abstract (English): ANNOTATION of the dissertation work of Kaliyekperova Kamila Bakhtzhankyzy «Study of the effect of variations in the phase composition of iron-containing nanocomposites on their hyperthermic properties and cytotoxicity», submitted for the degree of Doctor of Philosophy (PhD) in the educational program «8D07140-Nanomaterials and Nanotechnology» Relevance of the dissertation research. The rapid development of nanotechnology in the modern world encompasses virtually all areas of life, providing new approaches and technological solutions for scientific, technical, and applied problems. Nanostructured materials and composites having a set of unique physical and chemical properties having significant differences from macroscopic analogues are of particular interest. First of all, these features are associated with a high ratio of specific surface area to volume, quantum-size effects, as well as the ability to control the structural and functional properties of materials during their synthesis. It should be noted that in recent years, considerable attention has been paid to the use of nanostructured composites, in particular magnetic iron-containing or ferrite nanostructures in the biomedical field. This is primarily due to high biocompatibility, surface functionalization capabilities, and good controllability in magnetic fields. One of the most promising areas of research into the applicability of magnetic nanostructures is the targeted delivery of drugs using magnetic nanoparticles, which can increase the effectiveness of therapy by reducing drug dosage and minimizing side effects by localizing the active substance directly to the pathological lesion. Great attention to ferrite and iron-containing nanostructures in recent years is reflected in the expansion of their applicability in the field of magnetic hyperthermia. Ferrite nanoparticles such as MnFe2O4, CoFe2O4, ZnFe2O4 are able to efficiently convert the energy of an alternating magnetic field into heat in very short periods of time, thereby providing a local increase in temperature near and inside tumor tissues to therapeutically significant values (about 42-45°C). This temperature regime causes irreversible damage to malignant cells due to protein denaturation, disruption of the integrity of cell membranes, and suppression of DNA repair mechanisms. At the same time, healthy tissues, which have a more developed heat-dissipation system and resistance to thermal stress, are less susceptible to damage. The use of magnetic ferrite and iron-containing nanoparticles in magnetic hyperthermia allows for high selectivity and effectiveness in targeting tumor tissue, allowing this method to be considered both as a standalone treatment method and in combination with chemotherapy or radiation therapy, thereby increasing treatment effectiveness. An additional advantage of ferrite nanoparticles is the ability to fine-tune their heat-generating characteristics by varying the chemical composition, size, and morphology of the particles, as well as surface functionalization. Control of magnetic loss mechanisms, including Néel and Brown relaxation, allows optimization of specific absorption power, which in turn can be adapted to specific biomedical tasks, which makes ferritic nanostructures more preferable compared to traditional magnetite or hematite nanoparticles, which have limited efficiency of converting alternating magnetic field energy into thermal energy under conditions of clinically acceptable parameters. Also, magnetic iron-containing or ferrite nanoparticles find their practical application as contrast agents for medical imaging in magnetic resonance imaging due to their superparamagnetic properties and high magnetic susceptibility, which leads to a reduction in the longitudinal and transverse relaxation time of hydrogen nuclei, which in turn leads to an increase in image contrast and improved visualization quality of pathological changes in tissues compared to traditional contrast agents. It should be noted that ferrite magnetic nanostructures are universal functional elements of modern biosensor systems, providing high sensitivity, specificity and speed of analysis. Their further development opens up broad prospects for the early diagnosis of oncological and infectious diseases, monitoring of patient conditions, and the implementation of personalized approaches in medicine. Among the variety of iron-containing and ferrite nanostructures, zinc ferrite with a spinel type of structure and nanostructured composites based on it should be highlighted. Interest in this type of ferrite is primarily due to its exclusion of toxic heavy metal ions in its composition, which is one of the major advantages in the development of in vivo application systems. Compared to cobalt ferrite, which has high magnetic anisotropy and significant hysteresis losses, zinc ferrite has much lower magnetic anisotropy, which reduces the risk of uncontrolled local tissue overheating and makes it possible to use nanostructures for long-term or repeated hyperthermia procedures. At the same time, the high biocompatibility of zinc ferrite significantly simplifies the issues of toxicological assessment. In turn, the spinel structure of ZnFe2O4 is characterized by an ordered distribution of cations over the tetrahedral (A) and octahedral (B) positions of the crystal lattice, which determines the magnetic interactions between the sublattices and, consequently, the magnetic characteristics of the material. An important advantage of zinc ferrite is the possibility of isomorphic substitution of Fe2+/Fe3+ ions with Zn2+ ions in the crystal lattice, which allows for targeted control of magnetic anisotropy, coercive force, and saturation magnetization. The introduction of Zn2+ ions, which have a non-magnetic nature, leads to a redistribution of magnetic iron ions between the spinel sublattices, changing the exchange interactions and reducing the magnetic anisotropy of the system. This, in turn, promotes the formation of superparamagnetic behavior at small particle sizes, which is critical for biomedical applications involving the in vivo use of magnetic nanoparticles. In turn, the ability to fine-tune magnetic parameters by varying the degree of substitution of iron ions with zinc, as well as controlling the size and morphology of particles, allows adaptation of ZnFe2O4 nanostructures to specific biomedical applications. In particular, such nanomaterials demonstrate promising characteristics both for soft magnetic hyperthermia and for use in magnetic resonance imaging as contrast agents with controlled relaxation properties. However, it should be noted that despite the large number of works in this area, there are still many unresolved issues related to the study of the variability of the phase composition of ZnFe2O4 nanostructures, as well as its influence on resistance to external influences and the efficiency of change in the specific absorption power during hyperthermic application. The aim of the dissertation research. The aim of the dissertation research is to determine the effect of the variability of the phase composition of nanostructured iron-containing composites based on zinc ferrite on the change in its corrosion resistance, cytotoxicity, and efficiency of use in hyperthermic studies. Objectives of the dissertation research. Based on the stated aim of the dissertation research, the following objectives were formulated, the implementation of which made it possible to obtain new data on the prospects for the use of nanostructured composites based on zinc ferrite in the biomedical field. Ниже приведены сформулированные задачи, выполнение которых было осуществлено в диссертационном исследовании: The following are the formulated objectives that were implemented during the dissertation research: 1. Determination of the effect of variation in the ratio of components during the synthesis of nanostructured composites based on zinc ferrite on the phase composition and structural features. 2. Study of the kinetics of degradation processes of nanostructured composites in model buffer solutions and establishment of the influence of corrosion processes on cytotoxicity and efficiency of application in hyperthermia. 3. Study of the effect of exposure to ionizing radiation on the structural features and effectiveness of the use of ZnFe2O4 nanocomposites when used in magnetic hyperthermia. Objects of research. The objects of study were iron-containing composites based on ZnFe2O4 with a spinel structure, obtained by chemical precipitation and solid-phase synthesis followed by thermal annealing with a change in the ratio of oxide components, the change of which leads to a variation in the phase composition. Subject of research. The subject of the dissertation research is to establish patterns of change in corrosion resistance, cytotoxicity and hyperthermic efficiency of nanostructured iron-containing composites based on zinc ferrite depending on their phase composition, structural features and conditions of external influence, including the influence of aggressive biological environments and ionizing radiation. Research methods. The main methods for characterization of the studied samples of nanostructured composites were the scanning electron microscopy method for visualization of the morphological features of nanostructures; the X-ray diffraction method, used to determine the structural parameters, phase composition, and phase ratio in the samples, as well as to determine the degradation kinetics during corrosion exposure in the case of long-term exposure in model solutions; the method of determination of the efficiency of specific absorption power to determine the potential for application of nanostructures in hyperthermia; and the method of simulation of corrosion processes, which consists of placement of samples in model buffer solutions and their maintenance in established temperature conditions for specified time intervals. Cytotoxicity and biocompatibility were determined by MTT tests using Mia PaCa-2 cell lines and a solution (3-[4,5-dimethylthiazol-2yl]-2,5-diphenyltetrazolium bromide). Scientific novelty. The patterns of influence of the variability of the phase composition of nanostructured composites based on zinc ferrite, obtained by changing the ratio of oxide components, on their corrosion resistance in model biological environments have been established. During the studies conducted, it was determined that variation in the ratio of components leads to a change in the weight contributions of the main phase ZnFe2O4 and impurities in the form of ZnO and Fe2O3, as well as the degree of structural ordering and the degree of inversion characterizing the cation distribution in the spinel structure. The influence of the phase composition and structural features of nanocomposites on the efficiency of magnetic hyperthermia was revealed, including the contribution of interphase boundaries and defective structure to heat generation processes under the influence of an alternating magnetic field. During determination of the potential applicability of the studied (1-x)Fe3O4 – xZnO nanocomposites for hyperthermia, it was established that a change in the phase composition due to variations in the weight contributions of ZnFe2O4/ZnO in the composition and a decrease in size leads to an increase in the efficiency of the specific heat release rate from 80 W/g to 129 W/g, which makes it possible to consider these structures as one of the competitive materials in magnetic hyperthermia. The influence of ionizing radiation on the structural state, phase composition and hyperthermic efficiency of nanostructured composites based on ZnFe2O4 was studied, which expands the understanding of the possibility of their use in conditions of combined therapeutic effects. During the studies conducted, a direct correlation between the value of specific heat loss and the degree of radiation-induced structural degradation of nanocomposites, expressed through volumetric structural swelling and the accumulation of defects in the crystal lattice, was established. The established differences between trends in changes in structural parameters, as well as the specific heat release rate of samples of nanocomposites irradiated in model buffer solutions and without them, made it possible to conclude that the combined effect of the medium and ionizing radiation affects the rate of structural damage and, as a result, a decrease in the specific heat release rate. It is shown that irradiation in a PBS buffer solution leads to additional formation of chemically induced defects in the near-surface layer, which enhance the degradation of magnetic properties and the loss of specific heat losses compared to irradiation under dry conditions. The main provisions submitted for defense. 1. It was found that variation in the weight contributions of ZnFe2O4/ZnO in the composition of nanocomposites leads to an increase in the efficiency of the specific heat release rate from 80 to 129 W/g, due to a change in the degree of inversion, cation distribution and size effects associated with a decrease in grain size and specific surface area. 2. During experiments to determine the corrosion resistance of nanocomposites, it was found that the accumulation of amorphous and structurally disordered inclusions in the structure reduces the crystal-chemical stability of the spinel phase of ZnFe2O4 and promotes further redistribution of cations, enhancing the effect of cationic disorder, while an increase in the degree of inversion reflects the depth of these structural changes. 3. The assessment results of the influence of ionizing radiation on the structural stability of (1-x)Fe3O4 – xZnO nanocomposites showed that the displacement of the Fe2O3 phase from the composition of nanocomposites, as well as the formation of dislocation strengthening due to a change in particle size, leads to an increase in resistance to structural changes caused by ionization effects, which affect the effectiveness of hyperthermic application and cytotoxicity. 4. Optimal compositions of nanocomposites 0.56ZnFe2O4 – 0.44ZnO and 0.30ZnFe2O4 – 0.70ZnO, which have increased resistance to radiation exposure and maintain hyperthermic efficiency in conditions of therapeutic doses of radiation, were determined. Theoretical and practical significance of the research results. The role of alteration of the ratio of phases in composites based on zinc ferrite on the containment of corrosion processes during prolonged contact with buffer solutions has been determined, as well as the effect of formed ferrihydrite inclusions on the efficiency of applicability of nanostructures in magnetic hyperthermia has been established. Based on the studies carried out, optimal compositions of nanostructured composites based on zinc ferrite, which have great prospects for use in magnetic hyperthermia, as well as resistance to corrosion processes, have been determined. The proposed compositions of nanostructured composites can compete with ferrite nanostructures due to their high specific absorption power and high heating rate, while their resistance to ionizing radiation (gamma and electron radiation) opens up prospects for using these nanostructured composites as a basis for combined radiation therapy and magnetic hyperthermia. The results obtained form a scientific basis for the targeted design of ferrite nanocomposites with an optimal balance of corrosion resistance, biocompatibility, and functional efficiency for biomedical applications. Reliability of the results obtained. The main experimental works related to the study of the phase composition and structural features of (1-x)Fe3O4 – xZnO nanocomposites depending on the variation of the ratio of components in the composition were carried out in several parallels in order to eliminate measurement errors and establish errors and values of standard deviation. Conducting a series of reproducible experiments ensured the representativeness of the sample and allowed for a correct assessment of the reproducibility and stability of the identified structural patterns. The phase composition, as well as key structural parameters of the studied nanocomposite samples, including the crystal lattice parameters, the sizes of coherent scattering regions and the degree of crystallinity, were determined using modern instrumental analysis methods. All experiments were conducted on standardized and calibrated equipment using licensed software. Experiments with cellular structures were carried out in strict accordance with the methodological recommendations and ethical standards applicable to research of this nature. All procedures for sample preparation, experimentation, and results processing were aimed at ensuring the reproducibility, biological safety, and reliability of the data obtained. The use of artificial intelligence tools, in particular the ChatGPT software code, was employed to visualize the literature review data and to schematically represent various diagrams, charts, and research methods. The use of artificial intelligence technologies did not influence the acquisition of primary experimental data or replace traditional methods of scientific analysis but instead served as a tool for increasing the clarity and structure of the presented material. Personal contribution of the applicant. The synthesis of nanocomposites based on zinc ferrite compounds using chemical precipitation and mechanical grinding methods, as well as the development of nanocomposite production modes with varying component ratios, experimental work related to the study of the degradation kinetics of nanocomposites in model buffer solutions under various temperature conditions, and the determination of structural and morphological features were carried out by the applicant independently at the Laboratory of Engineering Profile of the L.N. Gumilyov Eurasian National University and the Laboratory of Solid State Physics of the Astana branch of the Institute of Nuclear Physics. Experiments related to the study of the prospects for the use of nanocomposites in magnetic hyperthermia and the determination of cytotoxicity were carried out jointly with employees of the Scientific and Practical Center for Materials Science of the National Academy of Sciences of Belarus and the Laboratory of Neutron Physics of the Joint Institute for Nuclear Research. All the main results of the experimental work, the determination of dependencies and their interpretation were carried out by the applicant together with scientific consultants. Connection of work with research projects and programs. Work related to the study of the kinetics of phase transformations with variations in the ratio of components in the composition of ferrite composites was carried out within the framework of the implementation of the tasks of program-targeted funding BR28713365 «Development of technological solutions in the field of creation and modification of structural materials for nuclear and alternative energy» (implementation period 2025-2027). Approbation of work. The main results of the research conducted as part of this dissertation were presented at international scientific conferences: ‒ The 11th International Youth Scientific Conference «Physics. Technologies. Innovations», dedicated to the 75th anniversary of the founding of the Institute of Physics and Technology (Yekaterinburg, 2024); ‒ the 5th international scientific forum «Nuclear Science and Technologies» (Almaty, 2024); ‒ 11th international conference dedicated to the 80th birth anniversary of Academician B.S. Yuldashev «Modern Problems of Nuclear Energy and Nuclear Technologies» (Tashkent, 2025). Publications. The main results of the dissertation research are presented in 6 scientific papers, of which 2 articles were published in journals indexed in the international databases Web of Science, Scopus, one article from the SHEQAC lists, three abstracts published in collections of scientific conferences. Structure and scope of dissertation research. The dissertation includes an introduction, four sections, a conclusion and a list of references. The dissertation is presented on 101 printed pages, includes 38 figures, 2 tables, 100 references. The introduction contains basic information about the relevance, aim and objectives of the dissertation research, as well as the scientific novelty, practical significance and main provisions submitted for defense. The first section of the dissertation presents the results of a literature review of the potential use of iron-containing and ferrite nanostructured composites in various industries, with an emphasis on the biomedical application of nanoparticles. The main emphasis in the review is to identify the main directions of development of the application of magnetic nanostructures in biomedicine, including hyperthermia, the interest in which consists in the expansion of the potential of application of ferrite composites, which are more efficient in heat generation under the influence of external magnetic fields compared to iron oxides. The results of a review of literature data on the toxicity and corrosion resistance of magnetic nanoparticles, which play a key role in the determination of the application potential and time frame for the use of nanoparticles, are also presented. The second section of the dissertation is devoted to the description of the main methods for characterizing the studied samples, as well as a description of experimental work related to the development of the synthesis of nanocomposites, the assessment of their stability to the effects of model buffer solutions, the determination of cytotoxicity, and the effectiveness of use in magnetic hyperthermia, as well as conducting experiments simulating the effect of ionizing radiation on changes in heat exchange processes and hyperthermia. The third section presents the results of the evaluation of phase transformations in (1-x)Fe3O4 – xZnO nanocomposites with variations in the ratio of components in the composition. Using the methods of scanning electron microscopy and X-ray diffraction and X-ray phase analysis, a comprehensive study of the dynamics of phase changes in the samples was carried out, and the main ratios at which the most optimal compositions of nanocomposites are formed for further research were determined. Much attention in the chapter is paid to the study of the mechanisms of corrosion and degradation of nanostructures when modeling the processes of their interaction with a model buffer solution at various temperature modes. The fourth section reflects the results of experimental work related to the study of the applicability of (1-x)Fe3O4–xZnO nanocomposites in magnetic hyperthermia, as well as reflecting the results of the assessment of the combined effect of ionizing radiation and model buffer solutions on the change in the hyperthermic efficiency of nanocomposites and heat exchange mechanisms. The Conclusion summarizes the main results of the conducted research and also reflects the results of the experimental work with a brief interpretation and conclusions.
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