Stable H3 peptide was delivered by gold nanorods to inhibit LSD1 activation and induce human mesenchymal stem cells differentiation

Abstract

// Xin Meng 1, * , Jianping Li 2, * , Minjuan Zheng 1 , Lei Zuo 1 , Chao Sun 1 , Yongsheng Zhu 1 , Ling Fang 1 , Liwen Liu 1 , Xiaodong Zhou 1 1 Department of Ultrasonography, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China 2 Department of Radiation Oncology, Xijing Hospital, Fourth Military Medical University, Xi’an 710032, Shaanxi, China * These authors contributed equally to this work Correspondence to: Xiaodong Zhou, email: zhouxdfmmu@tom.com Liwen Liu, email: liulwus@163.com Keywords: gold nanorods (AuNRs), hepatosis, stable peptide, LSD1, human mesenchymal stem cell (human MSCs) Received: January 11, 2017      Accepted: February 08, 2017      Published: February 18, 2017 ABSTRACT Recently, lysine-specific demethylase 1 (LSD1), which is the first identified histone demethylase, regulates post-translational modifications and has great promise as new targets for cancer and other diseases. Moreover, the ability of LSD1 to induce the differentiation of stem cells has attracted great attention in biological fields. In this study, we designed LSD1 peptide inhibitor based on its substrate H3 peptide. Through introducing a disulfide bond to stabilize the native peptide into alpha helical structure, we get a peptide with higher cell permeability and stability compared to its parent form. Using gold nanorods (AuNRs) as delivery systems to deliver stable peptide into human MSCs, the delivery efficiency has been enhanced significantly by flow cytometry and cell fluorescent imaging. The intracellular delivery of stable peptide by AuNRs-PEI-based nanocarriers could inhibit the activation of LSD1, which together with hepatocyte growth factor (HGF) exhibits obviously synergistic effect to induce human MSCs differentiation. Furthermore, the hepatic marker genes AFP (alpha fetal protein) and ck19 are up-regulated by AuNRs-stable peptide (AuNRs- SP- PEI) with HGF. In conclusion, our study is the first time to use stable H3 peptide to inhibit LSD1 activation, which has been further delivered by AuNRs as nanocarriers into human MSCs.