Triphala polyphenols-functionalized gold nanoparticles impair cancer cell survival through induction of tubulin dysfunction

Abstract Green-nanotechnology has enabled development of several potential nano medicines against diseases such as cancer. Triphala is an ayurvedic formulation with anticancer activities. . The aim of the study was to synthesis, characterize, and biologically evaluate the Trl-polyphenol-coated gold nanoparticles and to elucidate the mechanism of action of this novel formulation. Trl-GNPs were synthesized using the lyophilized powder of Trl extract and gold chloride trihydrate, and characterized by an assortment of spectroscopy techniques (UV-visible spectroscopy, energy-dispersive X-ray spectroscopy, transmission electron microscopy, Fourier-transform infrared spectroscopy, size- and zeta potential-analysis, and one-dimensional proton nuclear magnetic resonance spectroscopy). Cell viability analyses of the triple-negative breast cancer cell line, MDA-MB-231, were carried out using (3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) MTT assay. The nature of interactions of the Trl-GNPs with the purified tubulin was studied using spectrofluorimetry and circular dichroism. Microtubule architectural defects were investigated using immunofluorescence microscopy. Trl-GNPs were found to be inhibitory to the proliferative potential of the cells. The antiproliferative mechanism of action of Trl-GNPs involved perturbation of the structural the integrity of the mitotic-spindle-building protein, tubulin, at the secondary and tertiary levels. These disruptions of tubulin manifested as disrupted microtubule network in cells, facilitating mitotic arrest. Our data suggest a potential method for enhancing the delivery of Trl polyphenols to cancer cells, and elucidate the antiproliferative mechanism of action of these particles.