Demonstrating approaches to chemically modify the surface of Ag nanoparticles in order to influence their cytotoxicity and biodistribution after single dose acute intravenous administration

Abstract

With the advance in material science and the need to diversify market applications, silver nanoparticles (AgNPs) are modified by different surface coatings. However, how these surface modifications influence the effects of AgNPs on human health is still largely unknown. We have evaluated the uptake, toxicity and pharmacokinetics of AgNPs coated with citrate, polyethylene glycol, polyvinyl pyrolidone and branched polyethyleneimine (Citrate AgNPs, PEG AgNPs, PVP AgNPs and BPEI AgNPs, respectively). Our results demonstrated that the toxicity of AgNPs depends on the intracellular localization that was highly dependent on the surface charge. BPEI AgNPs (ζ potential = +46.5 mV) induced the highest cytotoxicity and DNA fragmentation in Hepa1c1c7. In addition, it showed the highest damage to the nucleus of liver cells in the exposed mice, which is associated with a high accumulation in liver tissues. The PEG AgNPs (ζ potential = −16.2 mV) showed the cytotoxicity, a long blood circulation, as well as bioaccumulation in spleen (34.33 µg/g), which suggest better biocompatibility compared to the other chemically modified AgNPs. Moreover, the adsorption ability with bovine serum albumin revealed that the PEG surface of AgNPs has an optimal biological inertia and can effectively resist opsonization or non-specific binding to protein in mice. The overall results indicated that the biodistribution of AgNPs was significantly dependent on surface chemistry: BPEI AgNPs > Citrate AgNPs = PVP AgNPs > PEG AgNPs. This toxicological data could be useful in supporting the development of safe AgNPs for consumer products and drug delivery applications.

• Acute toxicity
• pharmacokinetics
• protein sorption
• surface coating

Acknowledgements

We thank Prof. Vicki Stone and Prof. Igor Linkov for improving the manuscript and Dr. Jiefang Sun, and Dr. Zhe Wang, as well as Molecular and Environmental Toxicology Group help for technical support.

Declaration of interest

This work was funded by the National Science Foundation of China (Grant No. 21277168, 21321004, 21407162), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB14030401, XDB14030402), National Program on Key Basic Research Project (973 Program) (Nos. 2010CB933500 and 2011CB933401), the National Science Fund for Distinguished Young Scholars (Grant No. 11425520), Beijing Natural Science Foundation (No. 2152037), the China Postdoctoral Science Foundation Project (No. 2013M541056) and the European Union Seventh Framework Programme (Grant No. 604305, SUN). The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.

Supplementary material available online

Supplementary Figures S1-S5 and Tables S1--S2