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We have previously shown that GNPs are capable of inducing an antibody response in mice, which indicates that factors other than cytotoxicity may be involved and complicates in vivo application of GNPs. Nevertheless, most GNPs can enter cells efficiently, and most studies indicate that they are nearly harmless to cultured cells.
![increase intensity of anti stroke raman increase intensity of anti stroke raman](https://www.mdpi.com/biosensors/biosensors-08-00107/article_deploy/html/images/biosensors-08-00107-g005.png)
The uptake of GNPs is consistent with receptor-mediated endocytosis.
![increase intensity of anti stroke raman increase intensity of anti stroke raman](https://cdn.sanity.io/images/0vv8moc6/spectroscopy/6bbb5ad0c43a2db2677991176e22e578c5d69bf6-500x280.jpg)
The transport efficiency reaches a plateau 30 min after incubation.
![increase intensity of anti stroke raman increase intensity of anti stroke raman](https://bwtek.com/wp-content/uploads/2012/06/R-F-02.jpeg)
Uptake of GNPs reaches a maximum when the size nears 50 nm and when the aspect ratio approaches unity. GNPs enter cells in a size- and shape-dependent manner. The toxicity of GNPs has been investigated at the cellular level. However, the toxicity may be due more to the unique surface chemistry of the individual nanoparticle and less to the reduction in size per se. A large number of non-toxic bulk materials become poisonous when their size is reduced to nanoscale. Similarly, enhanced toxicity of titanium oxide nanoparticles has been reported and titanium oxide nanoparticles have been shown to induce oxidative stress in bacteria. Carbon black is nontoxic however, carbon nanotubes and fullerene are highly toxic when inhaled into the lungs. Recently, the increased toxicity of nanoparticles due to their tiny physical dimensions has been widely recognized. Gold nanoparticles (GNPs) may serve as a promising model to address this size-dependent toxicity, since gold is extraordinarily biocompatible. The environmental impact of nanoparticles is evident however, their nanotoxicity due to the reduction in size to nanoscale is rarely discussed. The toxicity of GNPs may be a fundamental determinant of the environmental toxicity of nanoparticles. This reduction in the toxicity is associated with an increase in the ability to induce antibody response. Modifying the surface of the GNPs by incorporating immunogenic peptides ameliorated their toxicity. The pathological abnormality was associated with the presence of gold particles at the diseased sites, which were verified by ex vivo Coherent anti-Stoke Raman scattering microscopy. Pathological examination of the major organs of the mice in the diseased groups indicated an increase of Kupffer cells in the liver, loss of structural integrity in the lungs, and diffusion of white pulp in the spleen. Injection of 5 and 3 nm GNPs, however, did not induce sickness or lethality in mice. The majority of mice in these groups died within 21 days. Starting from day 14, mice in this group exhibited a camel-like back and crooked spine. Mice injected with GNPs in this range showed fatigue, loss of appetite, change of fur color, and weight loss. GNPs of 3, 5, 50, and 100 nm did not show harmful effects however, GNPs ranging from 8 to 37 nm induced severe sickness in mice. Naked GNPs ranging from 3 to 100 nm were injected intraperitoneally into BALB/C mice at a dose of 8 mg/kg/week. Gold nanoparticles (GNPs) may serve as a promising model to address the size-dependent biological response to nanoparticles because they show good biocompatibility and their size can be controlled with great precision during their chemical synthesis. The environmental impact of nanoparticles is evident however, their toxicity due to their nanosize is rarely discussed.