Division of Chemistry and Biological Chemistry, School of Physical and Mathematical Sciences, Nanyang Technological University, 21 Nanyang Link, Singapore 637371, Singapore.
Institute of Molecular and Cell Biology, 61 Biopolis Drive, Singapore 138673, Singapore.
Nanoscale. 2017 Feb 9;9(6):2253-2261. doi: 10.1039/c6nr08869d.
Chronic heart failure is often characterized by the elevated amounts of reactive oxygen species such as hydrogen peroxide (HO) in the heart. Thus, it is of importance that selective release of therapeutic drugs occurs at the heart failure site to maximize therapeutic effects. In this work, functional mesoporous silica nanoparticles (MSNPs) were developed for detection of HO, selective drug release and controlled treatment toward heart failure. The HO-sensitive probe was attached to the surface of the MSNPs, and a therapeutic drug of heart failure, captopril, was loaded within the pores of the MSNPs and retained by the binding of α-cyclodextrin to the probe. HO present in tissue could react with the probe and enable the dissociation of α-cyclodextrin present on the nanoparticle surface, so that captopril could be successfully released along with "turn-on" of the probe fluorescence. In vivo experiments using the KillerRed heart failure transgenic zebrafish model demonstrated that this therapeutic system is physiologically responsive. Captopril-loaded MSNPs showed high therapeutic efficacy, improving the heartbeat rate and cardiac output in zebrafish experiencing acute KillerRed-induced heart failure.
慢性心力衰竭的特征通常是心脏中活性氧物质(如过氧化氢 (HO))的含量升高。因此,重要的是要使治疗药物选择性地在心力衰竭部位释放,以最大限度地提高治疗效果。在这项工作中,开发了功能性介孔硅纳米粒子 (MSNPs) 用于检测 HO、选择性药物释放和针对心力衰竭的控制治疗。HO 敏感探针附着在 MSNPs 的表面上,心力衰竭的治疗药物卡托普利装载在 MSNPs 的孔内,并通过 α-环糊精与探针的结合保留。组织中存在的 HO 可以与探针反应,使纳米粒子表面上存在的 α-环糊精解离,从而使卡托普利能够与探针荧光的“开启”一起成功释放。使用 KillerRed 心力衰竭转基因斑马鱼模型的体内实验表明,这种治疗系统具有生理响应性。载有卡托普利的 MSNPs 显示出很高的治疗效果,可提高经历急性 KillerRed 诱导的心力衰竭的斑马鱼的心跳率和心输出量。