Previous Page  17 / 40 Next Page
Information
Show Menu
Previous Page 17 / 40 Next Page
Page Background

16

Rkia El-kharrag

Department of Biology

College of Science

Dissertation

Title

Development of a Therapeutic Model of Early Liver Cancer Using Crocin-Coated Magnetite

Nano-particles

Faculty Advisor

Prof. Amr Amin

Defense Date

21 April 2015

Abstract

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 pa-tients 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 param-eters and coating materials have been investigated and characterized. Among

these parameters and coat-ing 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 60°C. After that

dex-tran-coated magnetite nanoparticles were bound to crocin, a pharmacologically active component of saf-fron,

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 con-taining 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 nanoparti-cles. 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 pro-liferation (Ki-

67), apoptosis (M30-Cytodeath and Bcl-2), inflammation (cyclooxygenase-2) and angiogen-esis (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.

Research Relevance and Potential Impact

Liver cancer is among the leading causes of cancer-related death at UAE and worldwide. As diagnosis and therapy continue to rep-resent

major challenges, in this thesis we encapsulated a major bioactive principal (crocin) of the commonly used spice “saffron” in magnetite

nanoparticles. Those crocin-loaded nanoparticles inhibited cell division of liver cells of cancer-induced mice and in human liver cancer cell line.

They also unregulated cell death and reduced inflammation and angiogenesis more efficiently than crocin alone. Thus, our engineered crocin-

nanoparticles is expected to have a potential clinical impact against liver cancer.

May 31, 2016
Dec 13, 2017
Nov 22, 2022