Stimuli-responsive polyvinylpyrrolidone-NIPPAm-lysine graphene oxide nano-hybrid as an anticancer drug delivery on MCF7 cell line

Abstract

Despite the advances in the development of chemotherapeutic agents, resistance to chemotherapy and adverse side effects are still big challenges against successful cancer treatment. To overcome these problems, one strategy is the application of nanomaterials and drug delivery systems to efficiently deliver the anticancer agents to tumour tissues with minimum toxic effects on healthy organs. In this study a graphene oxide nanohybrid (GO/NHs) was designed and fabricated for the delivery of chemotherapeutic agent fluorouracil (FU) to the breast cancer MCF7 cells. After preparation and characterization of GO/NHs, several biological analysis including haemolysis assay, cytotoxicity assay, cellular uptake, apoptosis assay, and protein expression were performed. The cytotoxic effects of FU, FU loaded GO/NHs (FU-GO/NHs), and blank GO/NHs was determined by MTT assay. The results of MTT assay showed no significant cytotoxicity for blank nano-hybrid on MCF7 cells. Furthermore, FU-GO/NHs were more cytotoxic than free FU. The uptake analysis results showed that developed nanocarrier could completely be internalized into the cells in the first hour. Besides, apoptotic effects and nuclear morphology changes of cells was evaluated by DAPI staining under fluorescent microscopy. Protein expression levels of p53, PARP, cleaved PARP, Bcl-2, and Bax were determined by western blot analysis. Western blot results showed higher levels of p53 and cleaved PARP after treatment with FU-GO/NHs, however, no substantial effect was observed for Bax and Bcl-2 protein concentrations.