Date of Award
Doctor of Philosophy (PhD)
Hepatocellular carcinoma is one of the most common health problems that is difficult to treat. As a result of the side effects frequently experienced with conventional cancer treatments, there has been a growing interest to develop controlled drug delivery system that can reduce the mortality rate of liver cancer patients and un-harm healthy tissues. Magnetite nanoparticles are potentially important in hepatocellular carcinoma treatment, since they can be used as delivery system. Pure and coated magnetite nanoparticles were synthesized via modified co-precipitation method in air at low temperature. Various reaction parameters and coating materials have been investigated and characterized. Among these parameters and coating materials, 1.0 % of dextran was selected as an optimum coating for nanoparticles using a slow feeding rate for the Fe2+/Fe3+ reactants, maintaining the stirring and soaking temperatures at 60ºC. After that dextran-coated magnetite nanoparticles were bound to crocin, a pharmacologically active component of saffron, via cross-linker. Crocin alone has shown anti-cancer activity in different in vitro and in vivo settings by several studies. The aim of this study was to synthesize dextran-coated magnetite nanoparticles containing crocin with a higher therapeutic index for hepatocellular carcinoma treatment. The nanoparticles with crocin were tested in vitro and in vivo for their anti-cancer effects as compared to free crocin. HepG2 cells treated with crocin-dextran-coated magnetite nanoparticles showed a decrease in cell proliferation compared to control (non-treated cells) or to those treated with free crocin or dextran-coated nanoparticles. The anti-cancer activity of crocin-dextran-coated nanoparticles was also evaluated in Balb/c mice. These mice were injected with carcinogenic agent, diethylnitrosamine. Histological examination revealed several precancerous changes. The immunohistochemical analysis using antibodies indication of cell proliferation (Ki-67), apoptosis (M30-Cytodeath and Bcl-2), inflammation (cyclooxygenase-2) and angiogenesis (vascular endothelial growth factor), indicated that magnetite nanoparticles conjugated with dextran plus crocin does indeed improve its anti-tumorigenic activity over free crocin. These results provide the basis for designing new modalities for treatment of liver cancer which could hopefully reduce its high mortality rate.
El-Kharrag, Rkia, "DEVELOPMENT OF A THERAPEUTIC MODEL OF EARLY LIVER CANCER USING CROCIN-COATED MAGNETITE NANOPARTICLES" (2015). Dissertations. 14.