CÚRAM Centre for Research in Medical Devices, Biomedical Sciences, National University of Ireland, Galway, Ireland.
Sci Rep. 2017 Oct 13;7(1):13138. doi: 10.1038/s41598-017-13744-y.
Reactive oxygen species (ROS) are key pathological signals expressed in inflammatory diseases such as cancer, ischemic conditions and atherosclerosis. An ideal drug delivery system should not only be responsive to these signals but also should not elicit an unfavourable host response. This study presents an innovative platform for drug delivery where a natural/synthetic composite system composed of collagen type I and a synthesized polythioether, ensures a dual stimuli-responsive behaviour. Collagen type I is an extracellular matrix constituent protein, responsive to matrix metalloproteinases (MMP) cleavage per se. Polythioethers are stable synthetic polymers characterized by the presence of sulphur, which undergoes a ROS-responsive swelling switch. A polythioether was synthesised, functionalized and tested for cytotoxicity. Optimal conditions to fabricate a composite natural/synthetic hollow sphere construct were optimised by a template-based method. Collagen-polythioether hollow spheres were fabricated, revealing uniform size and ROS-triggered nanoporation features. Cellular metabolic activity of H9C2 cardiomyoblasts remained unaffected upon exposure to the spheres. Our natural/synthetic hollow microspheres exhibit the potential for use as a pathological stimuli-responsive reservoir system for applications in inflammatory diseases.
活性氧 (ROS) 是癌症、缺血性疾病和动脉粥样硬化等炎症性疾病中表达的关键病理信号。理想的药物输送系统不仅应对这些信号做出响应，而且不应引起不利的宿主反应。本研究提出了一种用于药物输送的创新平台，其中由胶原蛋白 I 和合成的聚硫醚组成的天然/合成复合系统确保了双重刺激响应行为。胶原蛋白 I 是细胞外基质的组成蛋白，本身对基质金属蛋白酶 (MMP) 的切割有反应。聚硫醚是具有硫的稳定合成聚合物，其特征在于存在硫，硫会发生 ROS 响应的溶胀开关。合成了一种聚硫醚，并对其进行了功能化和细胞毒性测试。通过基于模板的方法优化了制造复合天然/合成空心球结构的最佳条件。制备了胶原蛋白-聚硫醚空心球，显示出均匀的尺寸和 ROS 触发的纳米孔特征。H9C2 心肌细胞的细胞代谢活性在暴露于球体时不受影响。我们的天然/合成空心微球具有作为用于炎症性疾病的病理刺激响应储库系统的应用潜力。
