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

Jing Xu, Mengxiao Yu, Chuanqi Peng, Phoebe Carter, Jia Tian, Xuhui Ning, Qinhan Zhou, Qiu Tu, Greg Zhang, Anthony Dao, Xingya Jiang, Payal Kapur, Jer Tsong Hsieh, Xudong Zhao, Pengyu Liu, Jie Zheng

Research output: Contribution to journalArticle

28 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)266-271
Number of pages6
JournalAngewandte Chemie - International Edition
Volume57
Issue number1
DOIs
StatePublished - Jan 2 2018

Keywords

  • biocompatibility
  • dose dependencies
  • nanoparticles
  • non-human primates
  • renal clearance

ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)

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    Xu, J., Yu, M., Peng, C., Carter, P., Tian, J., Ning, X., Zhou, Q., Tu, Q., Zhang, G., Dao, A., Jiang, X., Kapur, P., Hsieh, J. T., Zhao, X., Liu, P., & Zheng, J. (2018). Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non-human Primates. Angewandte Chemie - International Edition, 57(1), 266-271. https://doi.org/10.1002/anie.201710584