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Information × Registration Number 0213U003610, 0107U009687 , R & D reports Title The development of cytotoxic nanocomposites targeted transport systems and studying of the mechanisms of their action in the drug resistance overcoming popup.stage_title Розробка систем спрямованого транспорту цитотоксичних нанокомпозитів та вивчення механізмів їх дії в подоланні лікарської резистентності Head Chekhun Vasyl Fedorovych, Registration Date 08-02-2013 Organization R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology popup.description2 Результати НДР. We developed a new technology of synthesis of nanocomposite from magnetic fluid and cisplatin. We also created a system of static magnets for targeting and local accumulation of nanocomposite acting substance in tumor cells. Based on molecular biological, cytogenetical and cytomorphological studies in vitro and in vivo we proved advantages of the created antitumor nanocomposite compared to free form of cytostatic. For the first time we found genetic and epigenetic mechanisms of action of tested nanocomposite. It was proved that impact of nanocomposite on sensitive and resistant MCF-7 cells caused significant changes in p53, Bcl-2 and Bax expression, as well as miRNA-34a, which regulate apoptosis. The changes mentioned above cause elevation of number of cells in apoptosis. Also nanocomposite caused significant changes in MCF-7/S and MCF-7/Dox cells' invasion properties as a result of changes in expression of adhesion proteins (E-cadherin,N-cadherin, CD44 and ?-catenin) and reduction of miRNA-200b expression. It was never shown before that changes in endogenous iron homeostasis caused significant impact on apoptosis. Those changes included changes in methylation and expression of transferrin, its receptors, ferritin heavy and light chains (prdominantly in resistant cell line), which caused activation of free radical synthesis and to development of oxidative stress. Biochemical and biophysical studies showed that another stage in the chain of oxidative stress development in sensitive and resistant MCF-7 cells under nanocomposite impact is accumulation of free radicals and decrease of mitochondria functional activity. In vivo experiments proved that use of targeted delivery systems (combined action af nanocomposite and static magnetic field on sensitive and resistant to cisplatin Guerin carcinoma) elevated cytomorphological effects in tumor tissue, while its toxicity against vital organs is much more tolerant compared to cisplatin. Atom-adsorbtion spectroscopy studies showed that staticmagnetic field helps nanocomposite to penetrate into sensitive and resistant cells, elevating its antitumor effect. Also we found that changes in lipid content of tumor cells caused modifications of cellular membranes, elevating their permeability and elevating cisplatin levels in tumor. Absence of significant damage effect against general and biochemical blood counts and hepatocyte lipid content points on its low toxicity and possibility of its use as a vector in nanosystems for antitumor drugs delivery. Acquired data are fundamental basis for use of the target delivery systems for elevation of antitumor therapy effectiveness and overcoming of tumor drug resistance in oncological patients. Product Description popup.authors І. Л.Лісовський І.Є. Костецький І.М. Тодор В.В. Туров В.В.Бондар В.М.Півнюк В.Ф. Чехун Д.В. Демаш Л.А. Налєскіна Л.В. Трембач Л.З.Поліщук Л.М. Кунська М.М. Носко Н.А. Трегубова Н.В. Бородай Н.В.Маркєєва Н.В.Русецька Н.Й.Гуляй Н.М. Мельник Н.Ю. Лук'янова О.В. Юрченко П.П. Горбик Р.В. Луців Т.І. Стеблянко Т.В. Борікун Ю. О.Тимовська Ю.В. Лозовська popup.nrat_date 2020-04-02 Close