In vitro Evaluation of Zinc Oxide-Metformin Folic Acid Nanocomposite as a Targeted Drug Delivery System for Cancer Therapy.

BACKGROUND: Cancer has become the second cause of death worldwide after cardiovascular diseases. Thus, the development of efficient therapeutic approaches for cancer treatment seems necessary. One of the promising approaches is depending on nanotechnology in terms of drug delivery systems. ZnO nanoparticles have been approved for their efficiency as a drug delivery system due to their unique properties. Metformin (1, 1-dimethylbiguanide hydrochloride) is widely used as an anti-diabetic drug. However, recent studies have explored its repurposing as an anti-cancer drug. OBJECTIVE: The present study aims to evaluate the feasibility and efficiency of a folic acid-metformin ZnO nanoparticle delivery system in the treatment of melanoma and bladder cancer cell lines. METHODS: ZnO nanoparticles were chemically synthesized, loaded with metformin, and conjugated with folic acid at concentrations of 3% and 5%. Characterization of the nanoparticles was conducted using X-ray diffraction (XRD), Fourier-transform infrared spectroscopy (FTIR), dynamic light scattering (DLS), zeta potential analysis, and transmission electron microscopy (TEM). The cytotoxicity of ZnO nanoparticles was evaluated against human melanoma (A375) and bladder cancer (T24) cell lines via the MTT assay, with the determination of the half-maximal inhibitory concentration (IC50). RESULTS: ZnO nanoparticles were successfully synthesized with a spherical shape, size < 20 nm, and high homogeneity. Encapsulation efficiency of metformin on ZnO nanoparticles ranged from 95% to 98%. The folic acid-metformin ZnO nanoparticles demonstrated significant cytotoxic effects against both A375 and T24 cell lines in a dose-dependent manner. The IC50 values revealed higher sensitivity of T24 bladder cancer cells compared to A375 melanoma cells. CONCLUSION: Overall, our study highlights the promise of the ZnO-metformin-folic acid nanoparticles as an efficient drug delivery system for cancer treatment. These results open up a potentially valuable line of novel therapeutic applications.