Chen Jerry J Y, van der Vlies A J, Hasegawa U
Osaka University, Department of Applied Chemistry, 2-1 Yamadaoka, Suita 565-0871, Osaka, Japan.
Kansas State University, Tim Taylor Department of Chemical Engineering, 1005 Durland Hall, 66506, Manhattan Kansas, USA.
Polym Chem. 2020 Jul 21;11:4454-4463. doi: 10.1039/d0py00495b. Epub 2020 Jun 16.
Hydrogen sulfide (HS), an important gaseous signalling molecule in the human body, has been shown to be involved in many physiological processes such as angiogenesis. Since the biological activities of HS are known to be significantly affected by the dose and exposure duration, the development of HS delivery systems that enable control of HS release is critical for exploring its therapeutic potential. Here, we prepared polymeric micelles with different HS release profiles, which were prepared from amphiphilic block copolymers consisting of a hydrophilic poly(-acryloyl morpholine) segment and a hydrophobic segment containing HS-releasing anethole dithiolethione (ADT) groups. The thermodynamic stability of the micelles was modulated by altering the ADT content of the polymers. The micelles with higher thermodynamic stability showed significantly slower HS release. Furthermore, the sustained HS release from the micelles enhanced migration and tube formation in human umbilical vein cells (HUVECs) and induced vascularlization in the chick chorioallantoic membrane (CAM) assay.
硫化氢(HS)是人体内一种重要的气体信号分子,已被证明参与许多生理过程,如血管生成。由于已知HS的生物活性会受到剂量和暴露持续时间的显著影响,因此开发能够控制HS释放的递送系统对于探索其治疗潜力至关重要。在此,我们制备了具有不同HS释放曲线的聚合物胶束,这些胶束由两亲性嵌段共聚物制备而成,该共聚物由亲水性聚(丙烯酰吗啉)链段和含有释放HS的茴香脑二硫代硫酮(ADT)基团的疏水性链段组成。通过改变聚合物的ADT含量来调节胶束的热力学稳定性。具有较高热力学稳定性的胶束显示出明显较慢的HS释放。此外,胶束持续释放HS增强了人脐静脉细胞(HUVECs)的迁移和管形成,并在鸡胚绒毛尿囊膜(CAM)试验中诱导血管生成。