The Improved Cytotoxic Capacity of Functionalized Nanodiamonds with Metformin in Breast and Ovarian Cancer Cell Lines

Abstract

Nanodiamonds (ND-COOH) are used as drug delivery systems because of their attractive properties, as they allow for optimized transport of therapeutic agents in cellular models. Metformin (MET) is a drug used in diabetes mellitus therapy and exhibits anti-cancer properties. In this study, dispersed nanodiamonds were functionalized with metformin by directly binding them to 1,6-hexanediol (ND-MET), and their effects on the cytotoxicity of breast and ovarian cancer cells were evaluated in vitro. A simple synthesis of ND-MET was performed and characterized using FT-IR, XPS, Boehm titration, RAMAN, XDR, TEM, and dynamic light scattering (DLS). Data showed an increased intensity of the C-N bond band, indicating the presence of metformin in ND-MET. We detected signals at 1427 cm−1 and 1288 cm−1 corresponding to the C-N and C-H bonds, and adsorptions at 1061 cm−1 and 3208 cm−1 corresponding to the N-O and N-H bonds, respectively. The deconvolution of the C1s binding energy was also found at 286.24 eV. The biological effects of ND-MET were tested in both SKOV3 ovarian cancer and Hs-578T and MDA-MB-231 triple-negative breast cancer cell lines. In SKOV3 cells, the IC50 for the ND-MET complex was 35 ± 14 µg/mL, while for Hs-578T and MDA-MB-231 breast cancer cells, the IC50 for ND-MET was 759 ± 44 µg/mL and 454 ± 49 µg/mL, respectively. Our data showed that ND-MET could be used as an intracellular delivery system for metformin in cancer cells. Cell viability assays evidenced a reduced viability of all cell lines in a time and dose-dependent manner, with a significant sensitivity observed in SKOV3 ovarian cancer cells treated with ND-MET.