Potential multifaceted applications of cisplatin-loaded Camellia sinensis extract/CuO nanoparticles in cytotoxic and apoptotic effects

In recent years, the development of green multifunctional nanoformulations with specific anticancer activity has gained importance among scientists. In the present study, Camelia sinensis extract/CuO nanoparticles (CSE/CuO NPs) and cisplatin (Cis)-loaded CSE/CuO NPs were prepared and characterized by various TEM, XRD, FTIR, and UV-Vis techniques. The antioxidant properties of the green CSE/CuO NPs were evaluated using the CUPRIC Reducing Antioxidant Capacity (CUPRAC) and 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS)/HRP methods. The drug release profile of the NPs was studied at pH 7.4 and pH 5.5. Additionally, the cytotoxic effects of CSE/CuO NPs and Cis-loaded CSE/CuO NPs on MIA-PaCa-2 pancreatic cancer were evaluated using the MTT assay and compared with normal HUVEC cells. Subsequently, the apoptotic activity of CSE/CuO NPs and Cis-loaded CSE/CuO NPs on MIA-PaCa-2 cells was evaluated using Annexin-V FITC, and their effects on multi-drug resistance were determined using the ABCG2 antibody by flow cytometric analysis. Our results showed that Cis-loaded CSE/CuO NPs exhibited a pH-sensitive drug release profile. CSE/CuO NPs were highly cytotoxic to MIA-PaCa-2 pancreatic cancer cells, while exhibiting very low cytotoxicity to HUVEC cells. Moreover, CSE/CuO NPs and Cis-loaded CSE/CuO NPs were found to have higher apoptotic activity and lower drug resistance compared to free Cis. Although many studies have been conducted with CSE, this study was the first to show that CSE/CuO NPs were dominantly and selectively effective against pancreatic cancer, and resistance to Cis and its side effects could be significantly reduced by CSE-derived nanocarriers. Additionally, for the first time, the antioxidant property was investigated by applying CUPRAC and ABTS methods.