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.
Highlights
Nanotechnology is one of the key emerging technologies and has enormous potential to contribute to innovation, which fosters large investments in developing new industrial applications
Cell viability and intracellular localization of AgNPsin Hepa1c1c7 ATP assays to assess the toxicity of Citrate AgNPs, PEG AgNPs, PVP AgNPs, BPEI AgNPs and Ag+ to Hepa1c1c7 cells showed that BPEI AgNPs showed very high toxicity(EC50 10.38 mg/ml)
The results indicated that the high spleen PEGAgNPs uptake is highly dependent on the PEG coating because near neutral potential value, hydrophilic and steric repulsion of PEG can effectively prevent the opsonin–NPs interaction andprolong blood half-life of NPs, which could reach other mono- nuclear phagocyte system, such as the spleen (Li & Huang, 2008).The high body burden of PEG AgNPs in spleen and BPEI AgNPs in lung did not induce significant pathological changes based on the histopathology analysis (Supplementary Figure S4 and Table S2), indicating that the damage of AgNPs to mice was not directly relevant to the bioaccumulation of AgNPs in tissues and suggesting that PEG AgNPs could be used in splenic targetingof drug delivery
Summary
Nanotechnology is one of the key emerging technologies and has enormous potential to contribute to innovation, which fosters large investments in developing new industrial applications. This is reflected in the increasing number of nanotechnology-based products that reach the market (Nanodb.dk). A numberof studies have shown that AgNPs can be taken up by living organisms, where they migrate to the liver, spleen, lungs, kidneysand brain to induce apoptosis, membrane damage, inflammation and DNA damage (Gliga et al, 2014; Mahmood et al, 2010; Sharma et al, 2014; Suliman et al, 2015; Yang et al, 2012; Yinet al., 2013; Yu et al, 2013). These data have demonstrated that reactive oxygen species, oxidative stress and modified inflammatory responses play an important role in its animal and cellular toxicity (Chen et al, 2014; Farkas et al, 2011; Singh & Ramarao,2012; Walkey et al, 2014; Xue et al, 2012; Yin et al, 2013;Yu et al, 2013)
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