Dose-dependent phenomena in pharmacokinetics and clearance are well recognized in clinically used small molecules, however, very few studies have been conducted to investigate the dose-dependent behaviors of nanomedicines. Here we report our most recent study on dose-dependencies of renal clearable gold nanoparticles (GS-AuNPs). We found that pharmacokinetics and renal clearance are strongly dose-dependent when the injection doses are above 15 mg/kg: high dose accelerated the renal elimination and shortened the blood retention. As a result, the no-observed-adverse-effect level (NOAEL) of GS-AuNPs was above 1000 mg/kg in CD-1 mice. The rapid renal clearance and high biocompatibility 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 findings and fundamental understandings of dose effects on <i>in vivo</i> transport of ultrasmall AuNPs suggest a strategy to optimize their biomedical functions and minimize their health hazard in the future clinical translation.

Dose dependencies and biocompatibility of renal clearable gold nanoparticles: From mice to non-human primates

256th National Meeting (2018)

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