Unprecedented behavior of (9R)-9-hydroxystearic acid loaded keratin nanoparticles on cancer cell cycle.

Histone deacetylases, HDACs, have been demonstrated to play a critical role in epigenetic signaling and were found to be overexpressed in several type of cancers, therefore they represent valuable targets for anticancer therapy. 9-Hydroxystearic acid has been shown to bind the catalytic site of HDAC1, inducing G0/G1 phase cell cycle arrest and activation of p21WAF1 gene, thus promoting cells growth inhibition and differentiation in many cancer cells. Despite the (R) enantiomer of 9-hydroxystearic acid (9R) displayed promising in vitro growth-inhibitory effect on HT29 cell line, its scarce water solubility and micromolar activity require novel solutions for improving its efficacy and bioavailability. In this work, we describe the synthesis and in vitro biological profiling of 9R keratin nanoparticles (9R@ker) obtained through an in-water drug-induced aggregation process. The anticancer activity of 9R@ker was investigated in HT29 cell line: the results indicate an increased fluidity of cell membrane and a higher intracellular ROS formation, resulting in an unexpected S phase cell cycle arrest (25% increase as compared to the control) induced by 9R@ker as respect to free 9R and an induction of cell death.