Korniichuk N. Synthesis and properties of nanocomposites for application in local therapy of tumor diseases.

Українська версія

Thesis for the degree of Doctor of Philosophy (PhD)

State registration number

0823U100151

Applicant for

Specialization

  • 102 - Хімія

01-03-2023

Specialized Academic Board

ДФ 26.210.778

Chuiko Institute of Surface Chemistry of NAS of Ukraine

Essay

The aim of the work is the synthesis of new types of nanostructures promising for use in oncology, research of their physicochemical properties, adsorption activity of the surface in relation to topical cancer drugs, creation on this basis of nanotechnologies of models of new antitumor drugs, generalization and patenting of research results establishing directions of their practical application. Synthesis of multifunctional magnetosensitive nanocomposites (NC) Fe3O4/Al2O3/С with a carboncontaining surface, was performed by the method of low temperature pyrolysis of carbohydrates, there was carried out a carbonization of sucrose-containing coatings on the surface of NC Fe3O4/Al2O3. It is established that the used mode of heat treatment does not lead to deterioration of magnetic characteristics of magnetite, due to double modification of magnetite by aluminum isopropylate, and in its turn the carbonization of sucrose in these conditions is complete. The shape and size of NP of Fe3O4 and NC of Fe3O4/Al2O3 and Fe3O4/Al2O3/С were studied by the TEM method. It is established that the values of specific saturation magnetization of NC Fe3O4/Al2O3 and Fe3O4/Al2O3/С coincide with the corresponding changes in the mass fraction of magnetite in the structures. The results of TEM researches and magnetic measurements show the formation of NC Fe3O4/Al2O3 and Fe3O4/Al2O3/С on the “nucleus-shell” type. To explore the adsorption activity of the surface of carbon-containing NC Fe3O4/Al2O3/С, there was used a methylene blue. In order to identify the possibility of using the obtained NC as carriers for targeted transport of drugs in oncotherapy, the adsorption of anticancer drugs as cisplatin (CP), gemcitabine (GC) and doxorubicin (DR) on the surface of NC Fe3O4/Al2O3/С was studied. The adsorption processes were studied depending on contact time, pH of solution and concentration of the medicine. To model the adsorption kinetics, we used the Morris-Weber and Boyd diffusion models, the Lagergren pseudo-first-order model, the Ho and McKay pseudo-second-order model, and Elovich model. The adsorption isotherms of CP, GC and DR were analyzed by means of Langmuir and Freundlich models. The desorption of these drugs has been studied into saline solution with рН=5 (oncocell environment) and рН= 7,4 (human blood environment). The processes of adsorption and release of cisplatin from the surface of 60S bioglass were studied for further creation on its basis of a prototype of a new promising drug for topical use for prolonged complex chemotherapeutic and osteoconductive action. Magnetically sensitive colloidal vector systems were synthesized with the oncological preparation HC and the HER-2 antibody and with the bioactive bacterial cytotoxic lectin B. subtilis IMB B-772. Their effect on the viability of cancer cells (hormone dependent human breast adenocarcinoma with MCF-7 epithelial phenotype, three times aggressive breast carcinoma MDA-MB-231 with high proliferative and metastatic activity, hepatocellular carcinoma of the liver in HepG2) was investigated. Іncreased their cytotoxic activity to 23% due to the synergistic action of their components. The results of this work can be used in the development of new carriers of medicines, magnetically controlled adsorption materials for technical, technological, ecological and medical-biological purposes, medical test systems, theranostic means of targeted delivery and local therapy etc. Key words: adsorption, adsorption immobilization, magnetite, carbonization, multifunctional magnetosensitive nanocomposites, cisplatin, gemcitabine, doxorubicin, 60S bioglass, magnetic fluids, antitumor drugs.

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