In Vitro and In Vivo Investigation of Biosynthesized Copper Oxide Nanoparticles Using Rose Hip: Characterization and their Potential in Modulating Tubulin and VEGFR-II for Breast Cancer Therapy

Abstract

Breast cancer is a leading cause of death in women worldwide, and it is necessary to identify new and green therapeutic mechanisms. In this study, we are planning a green nanomedicine approach by synthesizing copper oxide nanoparticles (CuO NPs) using Rosa rugosa and evaluating them for anti-breast cancer activity. Using a green phytochemical approach, the stability, functionalization, and nanoscale characteristics of these Green CuO NPs were investigated using UV-Vis spectroscopy, FTIR, TEM, and zeta potential measurement. The CuO NPs showed strong cytotoxicity against MCF-7 and MDA-MB-231 breast cancer cell lines with IC₅₀ values of 6.98 ± 0.32 µg/mL and 21.33 ± 0.92 µg/mL, respectively, which is better than pure rosehip extract and doxorubicin. Mechanistic investigations revealed that CuO NPs caused G2/M cell cycle arrest, decreased tubulin levels to 62.4%, and enhanced cancer cell mortality (27.64 compared to 2.49% in controls), validating their microtubule-targeting efficacy. CuO NPs further exhibited strong anti-angiogenic activity via VEGFR-II downregulation. In vivo studies have also shown dose-dependent inhibition of the growth of Ehrlich Ascites Carcinoma (EAC) cells, a standard murine breast cancer model, by 66.7% at 5 mg/kg, with a decrease in tumor volume. Notably, oxidative stress markers improved and hepatic and renal functions were in normal levels, pointing toward the therapeutic safety of CuO NPs. This study emphasizes the potential of Green CuO NPs as an easy and eco-friendly nanomedicine strategy for the targeted therapy of breast cancer.