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Information × Registration Number 0215U003450, 0110U005964 , R & D reports Title The antitumor effect of chemotherapeutic drugs in their delivery of new nanocomposite carriers functionalized N-acylethanolamines popup.stage_title Head Hula Nadiya Maksymivna, Registration Date 02-02-2015 Organization A.V.Palladin Institute of Biochemistry of National Academy of Sciences popup.description2 The scientific report presents data on research priorities antitumor effect of chemotherapy drugs (doxorubicin) in their delivery of new nanocomposite carriers functionalized by N- acylethanolamines (NAEs). We studied the effects of individual components of the composite (N-stearoylethanolamine - NSE, N-palmitoylethanolamine - NPE and doxorubicin), and its combinations in the experiments as in vitro (on the cancer cells of human and animals) and in vivo in normal animals and animals with cancer. When studying NSE cytoprotective properties it was shown that NSE has different action relative to malignant and pseudonormal cells. NSE concentration of 10 (-5) M exhibits cytoprotective properties after prolonged incubation (48 h), together with the antitumor antibiotic doxorubicin in vitro. At the same time, NSE, but not NPE, exhibits antitumor activity against resistant to the action of estrogen breast cancer cell lines of human MDA-MD-231 (LC50 = 30 mkM) compared with estrogen-sensitivity cell line MCF-7 (LC50 = 50 mkM ). This indicates the important role of the fatty acid residue in the molecule at N-acylethanolamines selective implementation of these bioactive lipids malignant cells that are resistant to the action of estrogen. Furthermore, NSE in high concentrations (30 mkM) blocks the proliferation of leukemic cells in the G1 phase of the cell cycle through protein p27 Kіp1. This process is also accompanied by induction of apoptosis in malignant cells, as evidenced by early activation of caspase-7 and the cleavage of its substrate it - proteins PARP-1 - after 6 h actions of NSE. Study of the properties of the nanocomposite systems showed that immobilization of NSE and doxorubicin on polymeric carrier allows: 1) to effectively overcome the resistance of tumor cells to chemotherapy; 2) keep the cytoprotective activity NAEs in vitro; 3) significantly enhance the antitumor activity of doxorubicin. In in vivo studies revealed that the composite functionalized NSE can significantly reduce the toxic effects of doxorubicin on the body of tumor-bearing animals, without compromising its cytostatic effect on the tumor. The cytostatic effect of the composite is shown at a much lower concentration of doxorubicin in the composite, as compared with the action of free doxorubicin. In this application the composite NSE in experimental models of lymphoma and leukemia in mice resulted in complete recovery of tumor-bearing animals. Thus, the combination of N-stearoylethanolamine and doxorubicin on one platform in the form of drug delivery nanocomposite can simultaneously solve two fundamental problems of cancer chemotherapy - 1) reduced effective dose of the chemotherapeutic agent and 2) protection of normal cells from the adverse effects of these drugs by cytoprotectant molecules NAE. All this points to significant application prospects doxorubicin-NSE-nanocomposite systems in clinical practice. Product Description popup.authors Асмолкова В.С. Базилянська В.Р. Бердишев А.Г. Воєйков А.М. Глухова В.М. Горідько Т.М. Гудзь Є.А. Кіндрук Н.Л. Клімашевський В.М. Косякова Г.В. Мегедь О.Ф. Микоша О.С. Митрофанова Л.О. Онопченко О.В. Панчук Р.Р. Скорохід Н.Р. Стойка Р.С. Хмель Т.О. Чумак А.А. popup.nrat_date 2020-04-02 Close