تحضير وتقييم جسيمات الذهب النانوية المقترنة بالتراستوزوماب كدواء لخلايا سرطان الثدي المختبرية == Synthesiis and Evalluatiion of Nanogolld Biioconjugated wiith Trastuzumab as a Drug for Human Breast Cancer Cellll Liine
Author name:
اكتفاء مزهر عبد كسار الحسناوي
Supervisor name:
فاتن فاضل القزاز | بان عباس عبد المجيد
General topic:
Chemistry
Specific topic:
Analytical Biochemistry
Degree:
Doctorate
University:
Mustansiriyah University - College Of Science
Language:
English
University location:
Baghdad
First pages:
25T1713 - p.pdf
Abstract:
Breast cancer had been registered as the first order of cancer's leading cause of carcinoma death among Iraqi women. There are different trials to use bionanotechnology in medicine especially in the treatment of breast cancer.This work aimed to use different types of gold nanoparticles (GNPs) in application and evaluation of breast cancer cell through the following parts : - Part I : Synthesis three types of GNPs included : 1 - Gold nanospheres (GNspheres) by modification of the chemical method and using different reducing agent (sodium borohydride then capping with glutathione (GSH), the other method by using GSH and the last using new reducing agent (2 - Oxoglutaric acid). To the our present knowledge, this is the first report about using 2 - Oxoglutaric acid as reducing agent in the synthesis of GNspheres.2 - Gold nanorods (GNRs) by using seed - mediated growth method capped with cetyl trimethyl ammonium bromide (CTAB).3 - Gold nanoshells (GNSs) by using silica nanoparticles as core and seeded with gold as shell (silica - gold core shells).All the prepared types GNPs were characterized by using eight different techniques including : Atomic force microscopy (AFM), Transmission Electron Microscope (TEM), Field Emission Scanning Electron Microscopy (FESEM), UV - Vis spectroscopy, Dynamic light scattering (DLS), Fourier Transform Infrared (FTIR), Inductively Coupled Plasma - Optical Emission Spectrometry (ICP - OES), and zeta nanosizer. The measurements were done in Tarbiat Modares University (Faculty of Medicine and Faculty of Biological sciences) and Tehran University in Islamic Republic ofIran, except the techniques of ICP - OES it was done in Al - Sulaimani University and that of AFM was accomplished in the Ministry of Science and Technology in Iraq .Part II : This part includes two steps : 1 - Biofunctionalization i.e., modification of the surfaces of the three types of prepared GNPs by coating with thiol - poly ethylene glycol - carboxy (SH - PEG - COOH) then activation of the carboxyl group by adding 1 - ethyl - 3 - (3 - dimethyl aminopropyl) Carbodiimide hydrochloride (EDC) and N - Hydroxysuccinimide (NHS) using cross - linking reaction.2 - Bioconjugation i.e., binding the modified GNPs with the anti - Her2/neu antibody (Trastuzumab).All the above products were characterized by using UV - Vis spectroscopy, FTIR, and zeta nanosizer techniques .Part III : Application of the above novel products ( three types GNPs, biofunctionalized GNPs and bioconjugated GNPs, as well as trastuzumab alone ) on human breast cancer cell line (SK - BR - 3) and on an isolated fraction of whole blood, peripheral blood mononuclear cells (PBMCs) in vitro. The evaluation was done by cytotoxicity assay, viability assay using inverted and light microscopy, and ELISA - reader . Part IV : In clinical characterization of the disease two tumor marker [cancer antigen (CA15 - 3) and carcinoembryonic antigen (CEA)] were investigated as well as , sex steroid hormones (estradiol, progesterone, and testosterone ), lipid profile and total proteins in sera of (100) Iraqi women with breast cancer classified to two groups depending on their Her2/neu immunohistochemistry status (group I (positive) and group II (negative)) patients were recruited Al - Amal Hospital in Baghdad city during theperiod from the beginning of June - 2013 to end of Dec. - 2013. Their ages ranged from (27 - 70) years with irregular of menstrual cycle because taking of hormonal therapy. The results were compared with (40) blood samples from apparently healthy women as control group.Results revealed a highly significant increase (p<0.001) in the levels of CA15 - 3 and decrease in CEA. The three sex steroid hormones revealed significant increase (p<0.001) in the patients group compared to the control group. Lipid profile and total proteins were significantly decreased (p<0.05) in negative Her2/neu group and increased in positive Her2/neu, except triglyceride. It was concluded that there was a positive associations between CA15 - 3 and CEA as well as between CA15 - 3 and estradiol in group I, while in group II there was only a positive correlation with CEA. Non - significant (p>0.05) correlation were observed between two groups (I&II) for all biochemical parameters study
