Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University , No. 250, Wuxing Street., Taipei 11031, Taiwan.
Division of Nephrology, Department of Internal Medicine, Taipei Medical University Wan Fang Hospital , 111 Hsing-Long Road, Section 3, Taipei 11696, Taiwan.
ACS Appl Mater Interfaces. 2016 Aug 3;8(30):19691-700. doi: 10.1021/acsami.6b05905. Epub 2016 Jul 21.
Chronic kidney disease (CKD) is inflammation-related. Patients with chronic renal failure who undergo hemodialysis (HD) have some acute adverse effects caused by dialysis-induced oxidative stress, protein adsorption, platelet adhesion, and activation of coagulation and inflammation. Here, resonantly illuminated gold nanoparticles-modified artificial kidney (AuNPs@AK) for achieving high efficiency accompanying therapeutic strategy for CKD during HD is proposed. The efficiency in removing uremic toxins increased obviously, especially in the presence of protein (closer to the real blood). The excited AuNPs@AK expressed negatively charged surface reduced some acute adverse effects caused by dialysis-induced protein adsorption, platelet adhesion, and activation of coagulation, thus avoiding thrombosis during HD. Unlike to traditional HD which provides only one function of removing uremic toxins, the solution collected from the outlet of the sample channel of excited AuNPs@AK showed an efficient free radical scavenger that could decrease dialysis-induced oxidative stress. In the CKD mouse model, this antioxidative solution from excited AuNPs@AK further decreased fibronectin expression and attenuated renal fibrosis, suggesting a reduced inflammatory response. These successful in vitro and in vivo approaches suggest that resonantly illuminated AuNPs@AK in HD take multiadvantages in shortening treatment time and reducing risk of adverse effects, which promise trailblazing therapeutic strategies for CKD.
慢性肾脏病(CKD)与炎症有关。接受血液透析(HD)治疗的慢性肾衰竭患者会因透析引起的氧化应激、蛋白质吸附、血小板黏附和凝血及炎症激活而产生一些急性不良反应。在这里,我们提出了一种基于共振激发金纳米粒子修饰人工肾(AuNPs@AK)的策略,以实现高效伴随治疗 CKD 的策略。在存在蛋白质(更接近真实血液)的情况下,尿毒症毒素的去除效率明显提高。激发的 AuNPs@AK 表达出带负电荷的表面,降低了透析引起的蛋白质吸附、血小板黏附和凝血激活引起的一些急性不良反应,从而避免了 HD 期间的血栓形成。与传统 HD 仅提供一种去除尿毒症毒素的功能不同,从 AuNPs@AK 样品通道出口收集的溶液显示出高效的自由基清除剂,可降低透析引起的氧化应激。在 CKD 小鼠模型中,这种来自激发 AuNPs@AK 的抗氧化溶液进一步降低了纤连蛋白的表达,减轻了肾脏纤维化,表明炎症反应减轻。这些成功的体外和体内方法表明,HD 中的共振激发 AuNPs@AK 在缩短治疗时间和降低不良反应风险方面具有多种优势,为 CKD 的治疗策略提供了新的思路。