DEVELOPMENT OF A THERAPEUTIC MODEL OF PRECANCEROUS LIVER USING CROCIN-COATED MAGNETITE NANOPARTICLES

Amr Amin, Rkia El-Kharrag, Soleiman Hisaindee, Yaser Greish, Sheri F.M. Karam

Biology Department, UAE University, UAE

Abstract

The aim of this study was to develop an effective method for treatment of liver cancer using magnetite nanoparticles (MNPs) coated with crocin, the main active component of saffron. MNPs were coated with dextran and a cross-linker to enhance conjugation of crocin. Treatment of HepG2 cells with crocin-coated MNPs led to a significant inhibition of their growth as compared to control or those treated with free crocin or uncoated MNPs. Histological examinations of the livers of cancer-induced mice revealed several precancerous changes such as multiple proliferative hepatic foci, hyper- or dysplastic transformations of bile ducts/ductules, and vacuolation. Immunohistochemistry using antibodies specific for cell proliferation (Ki-67) and apoptosis (M30-CytoDEATH and Bcl-2) revealed their upregulation during development of precancerous lesions. Using antibodies specific for inflammation (cyclooxygenase-2), oxidative stress (glutathione) and angiogenesis (vascular endothelial growth factor) indicated the involvement of multiple signaling pathways in the development of precancerous lesions. Treatment with crocin-coated MNPs was associated with regression of precancerous lesions, significant upregulation of apoptotic cells and downregulation of Bcl-2 labeling and markers of cell proliferation, inflammation, oxidative stress and angiogenesis. In conclusion, crocin-coated MNPs are more effective than free corcin for treatment of liver precancerous lesions in mice. These findings will help to develop new modalities for early detection and treatment of liver precancerous lesions.

Keywords: Crocin, liver, cancer, nanoparticles.