Evaluating The Potential role of Targeted Nano-Particles and γ-Rays in Breast Cancer

Breast cancer continues to be the leading cause of cancer-related death in women worldwide. Quercetin a flavonoid has been reported to have anti-cancer potential and anti-proliferative effect on different cancer cell lines, both in vitro and in vivo. Quercetin is known to have modulatory effects on cell apoptosis, migration and growth via various signaling pathways. Though, quercetin possesses great medicinal value, its application as a therapeutic drug is limited due to some drawbacks like low oral bioavailability and poor aqueous solubility. These problems make quercetin an unreliable candidate for therapeutic purposes. Additionally, the rapid gastrointestinal digestion of quercetin is also a major barrier for its clinical translation. Hence, to overcome these disadvantages quercetin-based nano formulations are being considered in recent times. The aim of the research presented in this thesis was to develop quercetin in nano formulation with magnetic (Fe 304) NPs as a new targeted therapy for breast cancer treatment. The prepared QMNPs were spherical in shape and 40 nm in diameter. QMNPs reduced cell viability of MCF-7, HepG-2 and A 459 human cancer cell lines with IC 50 values 11 nmol/ml, 77.5 nM/ml and 104 nM/ml and exhibited anti proliferating effect via induction of G1l G0 cell cycle arrest and induction of ROS in MCF-7 cell lines. In vivo study demonstrated the anti tumor and radiosensitizing activity of QMNPs through enhancement of BRCA 1,2 gene expression down regulation of P 53, inhibition of PKA/PI3K/AKT/mTOR signaling pathway, suppression of inflammatory responses and mediating the altered immune responses followed by cell cycle arrest at G1/G0 phase consequently followed by induction of apoptotic cell death. QMNPs also exerted antioxidant properties through enhancement of the endogenous antioxidants and depression of lipid peroxidation.