Toxicity of silver nanoparticles in human macrophages: uptake, intracellular distribution and cellular responses

Abstract

Silver nanoparticles (SNP) are among the most commercialized nanoparticles worldwide. They can be found in many diverse products, mostly because of their antibacterial properties. Despite its widespread use only little data on possible adverse health effects exist. It is difficult to compare biological data from different studies due to the great variety in sizes, coatings or shapes of the particles. Here, we applied a novel synthesis approach to obtain SNP, which are covalently stabilized by a small peptide. This enables a tight control of both size and shape. We applied these SNP in two different sizes of 20 or 40 nm (Ag20Pep and Ag40Pep) and analyzed responses of THP-1-derived human macrophages. Similar gold nanoparticles with the same coating (Au20Pep) were used for comparison and found to be non-toxic. We assessed the cytotoxicity of particles and confirmed their cellular uptake via transmission electron microscopy and confocal Raman microscopy. Importantly a majority of the SNP could be detected as individual particles spread throughout the cells. Furthermore we studied several types of oxidative stress related responses such as induction of heme oxygenase I or formation of protein carbonyls. In summary, our data demonstrate that even low doses of SNP exerted adverse effects in human macrophages.

Nanosilver: new ageless and versatile biomedical therapeutic scaffold

“…326 The most common effects of AgNPs had been observed on erythrocytes, where they can lyse the membrane 327 and induce oxidative stressrelated responses such as induction of heme oxygenase I or formation of protein carbonyls. 328 AgNPs and the ions released from the oxidized nanosilver surface directly bind to sulfur-and phosphorus-containing cellular constituents such as proteins and DNA, potentially causing damage to cellular machinery. 234 The toxic effects of nanosilver on macrophages had been studied in the past.…”

In Vitro Study for Comparing the Cytotoxicity of Silver and Gold Nanospheres on Raw 264.7 Murine Macrophage Cell Line

“…Up to our knowledge, these data might be the first results for comparing the cytotoxicity of silver and gold nanospheres on RAW 264.7 murine macrophage cell line. Haase et al [23] showed that even the low doses of nano silver were highly toxic to human macrophage while treatment the cells with nanogold did not reveal significant toxicity even at higher concentration; the cells retained its viability up to 80% compared to control set. And Raymond et al [24] studied the cytotoxicity of silver nanoparticles (20 nm and 110 nm) on different cell line including two murine primary alveolar macrophages (C57Bl/6, and MARCO), they concluded that the small size of silver nanoparticles (20 nm) was more toxic to all cell lines and more active with THP1 macrophage compared to larger sized silver nanoparticles (110 nm).…”

Closing the gap: accelerating the translational process in nanomedicine by proposing standardized characterization techniques

“…42,44,45 Raman spectroscopy, in combination with microscopy, can prove particularly useful for characterization of nanomaterials that have heterogeneous surfaces. [46][47][48][49][50] WITec, a German company, has recently launched the first commercially available SEM-Raman instrument. 15 The general assumption with conventional Raman spectroscopy is that first-order scattering occurs at the "Brillouin zone", where the wave vector is zero.…”

“…It is a technique that is particularly relevant for toxicity studies because it does not require the use of fluorescent labels or staining procedures. [47][48][49][50] Fluorescent labels can alter the surface chemistry of the DDS, and such alterations can mask signs of toxicity exclusively due to the nanomaterial or potentially create toxicity that might not otherwise exist. Confocal-Raman is an instrument from which a substantial amount of information on the surface chemistry of the nanomaterial can be obtained.…”

“…Morphology, topology, and chemical composition can be determined for both metallic and soft matter nanoparticles with this instrument, revealing potential toxicity risks at a chemical level. [47][48][49][50] Nonclinical toxicology studies are required for all new drugs or DDS. These include single-dose and repeat-dose study designs.…”