Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non‐human Primates

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...

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Bibliographic Details
Published in:Angewandte Chemie International Edition 2018-01, Vol.57 (1), p.266-271
Main 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
Format: Article
Language:English
Subjects:
Biocompatibility
dose dependencies
Excretion
Gold
Injection
Intravenous administration
Kidneys
Nanoparticles
non-human primates
Pharmacokinetics
Pharmacology
Primates
renal clearance
Renal function
Toxicity
Transport
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Summary: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. Faster renal clearance at higher doses renders renal clearable gold nanoparticles (NPs) high biocompatibility in both mouse and non‐human primate models. Understanding the dose effect on the in vivo transport of ultrasmall gold nanoparticles opens up a pathway to maximize the biomedical potential of the NPs and to minimize their toxicity in future clinical translations.
ISSN:1433-7851
1521-3773
DOI:10.1002/anie.201710584