Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non‐human Primates. (5th December 2017)

• Record Type: Journal Article
• Authors: Xu, Jing; Yu, Mengxiao; Peng, Chuanqi; Carter, Phoebe; Tian, Jia; Ning, Xuhui; Zhou, Qinhan; Tu, Qiu; Zhang, Greg; Dao, Anthony; Jiang, Xingya; Kapur, Payal; Hsieh, Jer‐Tsong; Zhao, Xudong; Liu, Pengyu; Zheng, Jie
• Is Part Of: Angewandte Chemie. Volume 130:Number 1(2018)
• Page Start: 272
• Page End: 277
• Publication Date: 2017-12-05
• Subjects: Biokompatibilität -- Dosisabhängigkeit -- Nanopartikel -- Nicht-humane Primaten -- Renale Auscheidung; Chemistry -- Periodicals; 540
• DOI: 10.1002/ange.201710584
• Languages: English
• ISSNs: 0044-8249

Abstract

Abstract: While dose dependencies in pharmacokinetics and clearance are often observed in clinically used small molecules, very few studies have been dedicated to the understandings of potential dose‐dependent in vivo transport of nanomedicines. Here we report that the pharmacokinetics and clearance of renal clearable gold nanoparticles (GS‐AuNPs) are strongly dose‐dependent once injection doses are above 15 mg kg −1 : high dose expedited the renal excretion and shortened the blood retention. As a result, the no‐observed‐adverse‐effect‐level (NOAEL) of GS‐AuNPs was >1000 mg kg −1 in CD‐1 mice. The efficient renal clearance and high compatibility can be translated to the non‐human primates: no adverse effects were observed within 90 days after intravenous injection of 250 mg kg −1 GS‐AuNPs. These fundamental understandings of dose effect on the in vivo transport of ultrasmall AuNPs open up a pathway to maximize their biomedical potentials and minimize their toxicity in the future clinical translation.