Newly Modified Nanoformulation of Quercetin as Promising Chemotherapeutic Anticancer Agent

Abstract

Previous studies have demonstrated the potential anticancer effect of quercetin (QUR). However, water insolubility and less bioavailability of QUR reduce its efficiency in cancer therapy. So, this study aims to develop a nanoformulation of quercetin (QURnp) and evaluate its anticancer effect against Ehrlich ascites carcinoma (EAC)-bearing mice compared with native QUR. QUR- loaded pluronic nanoparticles (QURnp) were prepared and characterized. To investigate the anticancer effect of QUR and QURnp, histopathological, ultrastructural, immunohistochemical, cell cycle analysis, western blot, and qRT-PCR studies were performed on EAC tumor cells, as well as antioxidant biomarkers. The results showed that QURnp destroyed tumor cells and significantly elevated antioxidant status with the reduction in MDA and NO levels. QURnp caused mitochondrial degeneration in tumor cells. Furthermore, QURnp completely reduced tumor growth by inhibiting the IL-6/STAT3 signaling pathway, inducing cell cycle arrest at the G1/S phase via overexpression of p27 and suppression of angiogenesis via downregulation in VEGF gene expression. Moreover, immunohistochemical studies indicated that QURnp showed significant inhibition of proliferation marker Ki-67 and anti-apoptotic marker Bcl-2. This study demonstrated that QURnp is a promising anticancer agent superior to native QUR.