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Dose Dependencies and Biocompatibility of Renal Clearable Gold Nanoparticles
author: Zheng J, 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 JT, Zhao X, Liu P
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: 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 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 GS-AuNPs. These fundamental understanding 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

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PubYear: 2017
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Unit code: 152453
Publication name: Angewandte Chemie -International Edition
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Paper source: http://onlinelibrary.wiley.com/
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