1. Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non-human Primates
- Author
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Phoebe Carter, Xudong Zhao, Qinhan Zhou, Xuhui Ning, Qiu Tu, Jer Tsong Hsieh, Payal Kapur, Greg Zhang, Jing Xu, Jie Zheng, Chuanqi Peng, Jia Tian, Xingya Jiang, Anthony Dao, Mengxiao Yu, and Pengyu Liu
- Subjects
Biocompatibility ,Metal Nanoparticles ,Biocompatible Materials ,02 engineering and technology ,Pharmacology ,010402 general chemistry ,Kidney ,01 natural sciences ,Catalysis ,Article ,Mice ,Pharmacokinetics ,Species Specificity ,In vivo ,Animals ,Tissue Distribution ,Adverse effect ,No-Observed-Adverse-Effect Level ,Dose-Response Relationship, Drug ,010405 organic chemistry ,Chemistry ,General Medicine ,General Chemistry ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,Macaca fascicularis ,Colloidal gold ,Renal physiology ,Area Under Curve ,Toxicity ,Gold ,0210 nano-technology ,Clearance ,Glomerular Filtration Rate - 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.
- Published
- 2017