Williams Ryan M, Shah Janki, Tian Helen S, Chen Xi, Geissmann Frederic, Jaimes Edgar A, Heller Daniel A
From the Memorial Sloan Kettering Cancer Center, New York (R.M.W., J.S., H.S.T., X.C., F.G., E.A.J., D.A.H.); University of Massachusetts Medical School, Worcester (H.S.T.); and Weill Cornell Medical College, New York (X.C., F.G., E.A.J., D.A.H.).
Hypertension. 2018 Jan;71(1):87-94. doi: 10.1161/HYPERTENSIONAHA.117.09843. Epub 2017 Nov 13.
Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases.
直接靶向肾脏是提高治疗肾脏疾病药物治疗指数的一种有前景的策略。我们试图研究肾脏靶向中尺度纳米颗粒技术的肾脏选择性和安全性。我们发现,直接静脉注射这些颗粒可产生26倍的肾脏选择性,并且在肝脏或其他器官中的定位可忽略不计。纳米颗粒靶向肾近端肾小管上皮细胞,活体显微镜检查和体外成像证明了这一点。用纳米颗粒治疗的小鼠未表现出负面的全身影响、免疫反应、肝损伤或肾损伤。物质选择性地定位于肾小管的情况并不常见,这项工作预示着用于治疗肾脏疾病的肾脏靶向药物的开发。