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Theranostics 2020, Vol. 10, Issue 20 organ and the first-line barrier of the human body, can isolate the external pathogens from the internal environment. Topically applied AgNPs may induce cytotoxicity in the site and penetrate the skin and subsequently access the systemic circulation followed by adverse effects on other organs. For example, applying AgNPs gel and covering dressings will allow particles to penetrate and accumulate in the skin and produce potential cytotoxicity [315]. Before AgNPs, there are several reports on the skin toxicity of elemental silver, known as Argyria [316]. Argyria is a disease characterized by permanent gray-blue pigmentation of mucous membranes, eyes and skin, occurring in individuals exposed to high concentrations of silver for a long period. G D DiVincenzo et al. [317] previously reported that the skin of workers exposed to silver aerosols showed a distinctive gray bluish hue change, and deposited silver was also detected in worker’s hair, urine and feces. Jennifer et al. [318] reported a Argyria case. The patient showed uniform accumulation of silver on the skin after long-term consumption of silver solution. Current studies show that AgNPs can enter the hair follicles to induce local deposition and deposit into the subcutaneous structure by penetration pathways. The follicular penetration pathway is most commonly used to explain the penetration of particles into the 9017 skin [319-322]. Yu Kyung Tak et al. observed that AgNPs of different shapes would remain at different layers of skin. Rod-shaped, spherical, and triangular AgNPs penetrated the dermis, epidermis and stratum corneum layers, respectively. They observed the behavior of AgNPs in subcutaneous capillaries. And prolonged exposure time would increase the amount of nanoparticles. Notably, they found that the penetration of AgNPs was achieved by the follicular penetration pathway and intercellular penetration pathway [323]. Francesca et al. [324] attempted to use AgNPs to act on intact or damaged skin. They demonstrated a significantly higher penetration of AgNPs used on damaged skin as compared with intact skin, and they speculated that a small part of the particles would diffuse into the skin as silver ions. Radoslaw et al. [325] explored the cytotoxicity of AgNPs on epidermal keratinocytes (NHEK). The results showed that AgNPs inhibited cell proliferation and migration, induced activation of caspase 3 and caspase 7, and damaged DNA. In addition, by measuring the ATP content of cells treated with different concentrations (6.25, 12.5, 25 and 50 μg/ml), it was found that a high concentration of AgNPs significantly decreased the ATP production, and this phenomenon worsened with prolonging exposure time. Figure 5. A schematic of potential toxicities of AgNPs in the human body. The exposure patterns of AgNPs include respiratory inhalation, intravenous injection and skin contact. Affected organs include the eye, kidney, skin, and nerves, respiratory, immune, hepatobiliary and reproductive systems. Diseases or pathologic changes induced by AgNPs are listed. http://www.thno.orgPDF Image | Silver nanoparticles Synthesis medical applications safety
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