Optimizing the hybrid nanostructure of functionalized reduced graphene oxide/silver for highly efficient cancer nanotherapy

Abstract

Despite the development in cancer treatment, fabricating a targeted drug delivery system (DDS) that can effectively eliminate cancer cells still remains a challenge. In this study, we demonstrate the synthesis of a novel reduced graphene oxide–silver–ploy(L-lysine) (GPA) nanohybrid as an efficient platform for effective cancer nanotherapy. To investigate the morphology and chemical structure of GPA, transmission electron microscopy (TEM), X-ray diffraction (XRD) and Fourier transform infrared (FTIR) spectroscopy are used. The GPA nanohybrid was optimized in terms of temperature and time values using central composite design (CCD) and response surface methodology (RSM) to obtain the maximum amount of loaded silver nanoparticles (AgNPs) on the rGO surface. Introduction of ploy L-lysine (PLL) to the surface of rGO increased both the stability in aqueous solutions and cellular uptake of AgNPs. Then, Herceptin was chemically conjugated to the surface of the GPA nanohybrid and the Herceptin functionalized GPA (Her-GPA) was characterized using DLS and FTIR spectroscopy. A cytotoxicity assay was performed to assess the targeting capability and anticancer potential of the GO, rGO–Ag, GPA, Her-GPA and 5FU against MCF-7 and SK-BR-3 breast cancer cell lines which resulted in a dramatically higher potential of the Her-GPA to target and kill breast cancer cells, particularly HER2-positive cells. Moreover, the cellular uptake by SK-BR-3 cell lines provides supportive data for the potential application of Her-GPA as a novel targeted DDS. The results suggest that the Her-GPA can effectively be employed as a targeted DDS allowing intracellular AgNP delivery.