The actual task of oncology works well treatment of cancer while
The actual task of oncology works well treatment of cancer while causing a minimum harm to the patient. from 52 to 28?% in case of incubation with the Ezetimibe UDD-DOX in concentrations from 8.4-2.5 to 670-20?μg/ml and from 72 to 30?% after incubation with OLC-DOX. Simultaneously antibodies to epidermal growth factor maintained 75? % of the functional activity and specificity after matrix-assisted pulsed laser evaporation deposition. Thus the conclusion has been made about the prospects of selected new methods and approaches for creating an antitumor agent with capabilities targeted delivery of drugs. var. caesius in the 1970s. There are two proposed mechanisms by which doxorubicin acts in the cancer cell: (i) intercalation into DNA and disruption of topoisomerase-II-mediated DNA repair and (ii) generation of free radicals and their damage to cellular membranes DNA and proteins. In brief doxorubicin is usually oxidized to semi-quinone an unstable metabolite which is usually converted back to doxorubicin in a process that releases reactive oxygen species. Reactive oxygen species can lead to lipid peroxidation and membrane damage DNA damage and oxidative stress and triggers apoptotic pathways of cell death . According to the classification of chemotherapeutic brokers by mechanisms of action doxorubicin is referred to antimetabolites as far as it can intercalate with DNA and cytotoxic antibiotics of anthracycline family because it affects topoisomerase II enzyme . As a result doxorubicin significantly reduced the proliferation and survival of tumor cells. However Ezetimibe the cytotoxic activity of doxorubicin has no specificity which leads to serious side effects of the gastrointestinal tract liver and kidneys. It is noteworthy that such side effects inherent to the action of many anticancer drugs. We maintain opinion that answer is in usage of specific polymer materials which combine function of drugs vehicle and holder of antibodies to specific receptors of tumor cells. The possibility for receptor-dependent influence on tumor cells and targeted delivery of antitumor agent to cells with specific receptor profile is very attractive and encouraging area of anticancer research [22-25]. Based on earlier studies there was proposed the hypothesis of creating carbon-protein constructs for targeted delivery of drugs growth factors and biologically active substances CD14 on the base of carbon nanomaterials (CNMs). As a biologically inert basis for accession drug and tumor-specific antibodies we propose ultra dispersed diamonds (UDDs) and onion-like carbons (OLCs) [1 3 10 Thus the goal of our work was to syntheses antitumor nanocarbon-protein conjugates (NCPCs) on the basis of carbon “nucleus” (UDDs or OLCs) with specific antibodies to the tumor-specific receptor of epidermal growth Ezetimibe factor (EGFR) and antimetabolic anthracycline drug (doxorubicin (DOX)). The novelty of investigation idea is in combination of anti-proliferation properties of DOX and receptor-specific binding of antibodies to EGFR for targeted increasing concentration of DOX in tissue niches which over-expressed Ezetimibe of EGFR. In such way effectiveness of the antitumor treatment will be increased and level of hum full side effect will be minimized. As a biologically inert vehicle for accession DOX and anti-EGFR antibodies we propose to use UDD or OLC aggregates. Then methods of controlled releasing of DOX were tested. Due to estimated cellular responses on different concentrations of CNMs DOX NCPCs MCF-7 and HT29 cells viability was measured. Afterwards activity of antibodies to EGFR after matrix-associated pulse laser evaporated (MAPLE) deposition on carbon surface was analyzed. In the results obtained NCPCs allowed to realize sustained release of DOX and exhibited excellent dose-dependent cytotoxicity to tumor cells and biocompatibility in inactivated form. So these NCPCs with DOX represent a platform for targeted delivery and for cell-specific release of antitumor drugs. Methods Cell Lines Breast adenocarcinoma cell collection MCF-7 and hepatocellular carcinoma HT29 was kindly offered by the bank of cell lines of man and animals R.E.Kavetskiy’ Institute of Experimental Pathology Oncology and Radiobiology of NAS of Ukraine. Cells were incubated under standard conditions in 5?% of CO2 and 100?% humidity in RPMI-1640 medium (Sigma USA). Full medium was supplemented with 10?% fetal bovine serum (FBS Sigma USA) and 40?mg/ml gentamycin (Sigma) for cell.