Bulte Jeff W M, Schmieder Anne H, Keupp Jochen, Caruthers Shelton D, Wickline Samuel A, Lanza Gregory M
Russell H. Morgan Department of Radiology and Radiological Science, Division of MR Research and Cellular Imaging Section, Institute for Cell Engineering, the Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Department of Medicine, Division of Cardiology, Washington University Medical School, St. Louis, MO, USA.
Nanomedicine. 2014 Oct;10(7):1385-8. doi: 10.1016/j.nano.2014.05.001. Epub 2014 May 14.
Due to their small size, lower cost, short reproduction cycle, and genetic manipulation, rodents have been widely used to test the safety and efficacy for pharmaceutical development in human disease. In this report, MR cholangiography demonstrated an unexpected rapid (<5 min) biliary elimination of gadolinium-perfluorocarbon nanoparticles (approximately 250 nm diameter) into the common bile duct and small intestine of rats, which is notably different from nanoparticle clearance patterns in larger animals and humans. Unawareness of this dissimilarity in nanoparticle clearance mechanisms between small animals and humans may lead to fundamental errors in predicting nanoparticle efficacy, pharmacokinetics, biodistribution, bioelimination, and toxicity. From the clinical editor: Comprehensive understanding of nanoparticle clearance is a clear prerequisite for human applications of nanomedicine-based therapeutic approaches. Through a novel use of MR cholangiography, this study demonstrates unusually rapid hepatic clearance of gadolinium-perfluorocarbon nanoparticles in rodents, in a pattern that is different than what is observed in larger animals and humans, raising awareness of important differences between common rodent-based models and larger mammals.
由于体型小、成本低、繁殖周期短以及可进行基因操作，啮齿动物已被广泛用于测试药物开发对人类疾病的安全性和有效性。在本报告中，磁共振胆胰管造影显示钆全氟碳纳米颗粒（直径约250纳米）在大鼠体内意外地迅速（<5分钟）经胆汁排入胆总管和小肠，这与较大动物和人类的纳米颗粒清除模式明显不同。未意识到小动物与人类在纳米颗粒清除机制上的这种差异可能会在预测纳米颗粒的疗效、药代动力学、生物分布、生物消除和毒性方面导致根本性错误。临床编辑评论：全面了解纳米颗粒清除是基于纳米医学的治疗方法应用于人类的明确前提。通过磁共振胆胰管造影的新应用，本研究证明了啮齿动物体内钆全氟碳纳米颗粒的肝脏清除异常迅速，其模式与在较大动物和人类中观察到的不同，这提高了人们对常见啮齿动物模型与较大哺乳动物之间重要差异的认识。
