Synthesis of platinum nanoparticles functionalized with glutamine and conjugated with thiosemicarbazone and their cytotoxic effects on MDA-MB-231 breast cancer cell line and evaluation of CASP-8 gene expression.

Abstract

Breast cancer (BC) is the most prevalent form of cancer among women and is a major contributor to cancer-related fatalities. Nanotechnology has provided novel approaches to drug delivery to cancer cells. In this work, we synthesized platinum (Pt) nanoparticles, functionalized them with glutamine, conjugated them with thiosemicarbazone (TSC), and characterized their anticancer effects on the MDA-MB-231 breast cancer cell line. Characteristics of the nanoparticles were assessed by FT-IR, XRD, EDS mapping, SEM, TEM, DLS, and zeta potential measurement. Cell viability was characterized by MTT assay, and cell necrosis/apoptosis levels were determined by flow cytometry. The expression level of the CASP-8 gene was investigated by real-time PCR. Pt@Gln-TSC nanoparticles are spherical, 20-70 nm in diameter in dry form, 662 nm after hydration, and their zeta potential was - 6.6 mV. The 50% inhibitory concentration (IC50) for MDA-MB-231 (breast cancer) and HDF (normal) cell lines was 170 and 348µg/ml, respectively. Also, the IC50 of oxaliplatin drug and TSC on MDA-MB-231 cells was 184 µg/ml and 307 µg/ml, respectively. Treatment with Pt@Gln-TSC nanoparticles caused an increase in cell necrosis and primary apoptosis and elevated the expression of the CASP-8 gene by 2.54 folds. This study shows that Pt@Gln-TSC nanoparticles are significantly more toxic to breast cancer cells than to normal cells and can inhibit MDA-MB-231 cells by activating extrinsic apoptosis.