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 文獻名： Unprecedented Behavior of (9R)-9-Hydroxystearic Acid-Loaded Keratin Nanoparticles on Cancer Cell Cycle

作者： Alberto Busi,^a Annalisa Aluigi,^b Andrea Guerrini,^b Carla Boga,^a Giorgio Sartor, ^c Natalia Calonghi,^c Giovanna Sotgiu,^b Tamara Posati,^b Franco Corticelli,^d Jessica Fiori,^e Greta Varchi^b and Claudia Ferroni^b

^aDepartment of Industrial Chemistry, University of Bologna, Viale Risorgimento 4, 40136 Bologna, Italy

^bInstitute for the Organic Synthesis and Photoreactivity, National Research Council, Via Gobetti 101 - 40129 Bologna, Italy

^cDepartment of Pharmacy and Biotechnology, Via Irnerio 48, 40126 Bologna, Italy

^dInstitute for Microelectronics and Microsystems, National Research Council, Via Gobetti 101, 40129 - Bologna, Italy

^eDepartment of Chemistry “G. Ciamician”, University of Bologna, Via Selmi 2, 40126, Bologna, Italy

 

摘要：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 the p21WAF1 gene, thus promoting cell growth inhibition and differentiation in many cancer cells. Despite the (R) enantiomer of 9-hydroxystearic acid (9R) displaying a promising in vitro growth-inhibitory effect on the 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 the 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 with respect to free 9R and an induction of cell death.