Study the Anticancer Properties of Thymol-Loaded PEGylated Bovine Serum Albumin Nanoparticles Conjugated with Folic Acid.

Phenolic compounds such as Thymol have an effective role in suppressing cancer, however, their low solubility in aqueous solution has limited their use. This study aimed to prepare Thymol (TY)-loaded bovine serum albumin (BSA) nanoparticles surface-modified with polyethylene glycol (PEG) conjugated with folic acid (FA) and evaluate their inhibitory activity on cancer cells. The TY-BSA-PEG-FA was characterized using DLS, FESEM, and FTIR. The encapsulation efficiency (EE) was evaluated indirectly by using UV absorption. The antioxidant property of nanoparticles was evaluated by 2,2'-azinobis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH), and ferric reducing ability of plasm (FRAP) methods. The effects of nanoparticles against cancer cells were investigated by MTT, AO/PI, flow cytometry, and real-time qPCR methods. The results showed the spherical morphology of TY-BSA-PEG-FA with an average size of 70.0 nm, a PDI of 0.32, a zeta potential of -11.3 mV, and an EE of 89.0±2.3 %. The cytotoxicity effects of nanoparticles against all cell lines were in a concentration-dependent manner. AGS gastric cancer cells were reported to be the most vulnerable to treatment, while pancreatic cancer cells (PANC-1) and normal skin cells (HFF) would be the most resistant. The SubG1 phase arrest of about 66 % occurred at 85 μg/mL. An increase in apoptotic cells in fluorescent staining, along with decreased expression of Bcl-2 and increased expression of the BAX gene demonstrated the induction of apoptosis in treated cells. The powerful inhibitory effect of nanoparticles in inhibiting ABTS free radicals (IC =82 μg/mL) and DPPH free radicals (IC =844 μg/mL) and the ability to reduce iron ions indicated the antioxidant effects of TY-BSA-PEG-FA. Based on these results, the synthesized nanoparticles may be suitable for further investigation in the treatment of cancer, notably gastric cancer.