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Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles: From Mice to Non‐human Primates
Author(s) -
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 JerTsong,
Zhao Xudong,
Liu Pengyu,
Zheng Jie
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201710584
Subject(s) - pharmacokinetics , colloidal gold , in vivo , pharmacology , chemistry , biocompatibility , clearance , nanoparticle , renal physiology , biodistribution , adverse effect , excretion , biophysics , renal function , nanotechnology , in vitro , medicine , materials science , urology , biochemistry , biology , microbiology and biotechnology , organic chemistry
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.