Investigating the anticancer and anti-angiogenic effects of graphene oxide nanoparticles containing 6-gingerol modified with chitosan and folate

Abstract

Abstract Objective The use of nanocarriers to improve the targeting of treatment plays a key role in the treatment of many diseases, including cancer. This study was carried out to synthesize graphene oxide (GO) containing 6-gingerol (Ging) modified with chitosan (CS)-folic acid (FA) nanoparticles (Ging-GO-CS-FA) to improve the anti-cancer effects of Ging. Methods After the synthesis of nanoparticles, the average size, surface charge, and dispersion index (DPI) of nanoparticles were analyzed by the dynamic light scattering (DLS) method. Field emission scanning electron microscope (FESEM) and Fourier transform infrared spectroscopy (FTIR) were utilized to assess the morphology and functional groups of synthesized nanoparticles, respectively. The 2,5-diphenyl-2H-tetrazolium bromide (MTT) method was performed to assess the toxicity effect of nanoparticles on different types of cancer cells. The antioxidant power of nanoparticles was evaluated by ABTS and DPPH methods. In addition, the chorioallantoic membrane (CAM) test was conducted to investigate the anti-angiogenic effects of nanoparticles. Finally, the real-time quantitative PCR (qPCR) method was carried out to detect the changes in the expression of angiogenic and antioxidant genes in cancer cells. Results The nanoparticles have an average size of 73.21 nm, a DPI of 0.27, and a surface charge of 29.5. The encapsulation rate of Ging in nanoparticles was reported to be 81.7%. According to the MTT test, the most sensitive cell line to the Ging-GO-CS-FA nanoparticles was reported to be gastric cancer cells (IC50 ~ 27). The results of the antioxidant test showed the high antioxidant power of nanoparticles in the laboratory environment by inhibiting ABTS and DPPH free radicals. The pro-oxidant power of Ging-GO-CS-FA against cancer cells was confirmed by reducing the amount of the superoxide dismutase (SOD) gene in the treated cells. The decreasing effects of Ging-GO-CS-FA on angiogenesis were observed by reducing the average length, the number of blood vessels, average height, and weight of treated embryos. In addition, the decrease in the expression of VEGF and VEGF-R genes confirmed the anti-angiogenic of Ging-GO-CS-FA. Conclusions These results show the promising effect of Ging-GO-CS-FA on gastric cancer cells by inhibiting angiogenesis and increasing the level of oxidants.