Ricerc@Sapienza

Zinc oxide (ZnO) nanomaterials are used in a wide range of products ranging from cosmetics to fabric and electronic devices. In addition, some ZnO-derived nano and microparticles have been demonstrated to exert antibacterial properties. For their increased exposure, their potential harm to human health needs to be carefully investigated.
Our hypothesis is that treatment of tumor and non tumor cells with ZnONR causes a vicious pathogenetic circuit triggered and maintained by the following players: HIF-1a, activated by ZnRO coating and by ROS; and HMGB1, released by damaged and dying cells and acting as a paracrine cytokine.The link between HIF-1a and HMGB1 is represented by membrane receptors binding to HMGB1 and whose transcription is increased by HIF-1a.
To demonstrate it, in this study, we will use ZnO nanorods (ZnONR) obtained through the thermal decomposition method, to initially, determine their uptake, increase of intracellular Zn++ and ROS production. Next, we will determine the release of HMGB1 from damaged or dying cells, HIF-1a activation, as well as HIF-1a-dependent gene expression and metabolic reprogramming. In order to correlate ZnONR effects with tumor grade, we will use HaCat cells, a human immortalized keratinocyte cell line, and two breast cancer cell lines i.e. the non-metastatic and more differentiated MCF7 and the metastatic and poorly differentiated MDA-MB-231.
In conclusion, our study will delineate the mechanism of action of ZnONR on tumor and non tumor cells that will help to understand their safety for human health and rationalize their use in medicine.