Silver nanoparticles protect human keratinocytes against UVB radiation-induced DNA damage and apoptosis: potential for prevention of skin carcinogenesis

Abstract

Ultraviolet (UV)-B radiation from the sun is an established etiological cause of skin cancer, which afflicts more than a million lives each year in the United States alone. Here, we tested the chemopreventive efficacy of silver-nanoparticles (AgNPs) against UVB-irradiation-induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT). AgNPs were synthesized by reduction-chemistry and characterized for their physicochemical properties. AgNPs were well tolerated by HaCaT cells and their pretreatment protected them from UVB-irradiation-induced apoptosis along with significant reduction in cyclobutane-pyrimidine-dimer formation. Moreover, AgNPs pre-treatment led to G1-phase cell-cycle arrest in UVB-irradiated HaCaT cells. AgNPs were efficiently internalized in UVB-irradiated cells and localized into cytoplasmic and nuclear compartments. Furthermore, we observed an altered expression of various genes involved in cell-cycle, apoptosis and nucleotide-excision repair in HaCaT cells treated with AgNPs prior to UVB-irradiation. Together, these findings provide support for potential utility of AgNPs as novel chemopreventive agents against UVB-irradiation-induced skin carcinogenesis.

Comparative analysis of the relative potential of silver, Zinc-oxide and titanium-dioxide nanoparticles against UVB-induced DNA damage for the prevention of skin carcinogenesis

“…Topical sunscreens, mainly available as over the counter UVB protective agents, not only have failed in limiting the incidence of skin cancer, but are also of concern for their unintended harmful effects. This study compared the protective efficacy of titanium-dioxide (TiO2) and zinc-oxide (ZnO) nanoparticles (NPs) that are most common physical sun blockers in commercial sunscreens with that of Ag-NPs, the newly discovered UVB protective agents by us [17, 18]. …”

“…Moreover, citrate-coated Ag-NPs (up to 20 μg/mL) did not induce significant ROS generation in human bronchial epithelium cells (BEAS-2B) as compared to unirradiated cells [33]. Since our synthesized Ag-NPs are coated with trisodium citrate [18], so it could be one reason for their non-toxic and non-pro-oxidant nature.…”

“…Silver nitrate, sodium borohydride, sodium citrate tribasic dehydrates, 2’, 7’-dichlorofluorescin diacetate (DCFH-DA), Zinc-oxide nanoparticles (ZnO-NPs) and titanium-dioxide nanoparticles (TiO2-NPs) were purchased from Sigma-Aldrich (St. Louis, MO). Silver nanoparticles (Ag-NPs) were synthesized and characterized as described earlier [18]. Countess cell counting chamber slides and trypan blue were obtained from Life technologies (Grand Island, NY) and Thermo Scientific, respectively.…”

“…We recently demonstrated UVB protective effects of silver nanoparticles (Ag-NPs) in human immortalized keratinocytes (HaCaT) [17, 18]. Here our objective was to conduct comparative analysis of UVB protective efficacy of Ag-NPs against ZnO- and TiO2-NPs.…”

Drug delivery strategies for chemoprevention of UVB‐induced skin cancer: A review

“…Silver nanoparticles (AgNPs) have been used against UVB‐irradiation‐induced DNA damage and apoptosis in human immortalized keratinocytes (HaCaT) . Silver has been in use for centuries for the prevention and treatment of different diseases as well as in healing of skin wounds because of its exceptional free radical scavenging, antimicrobial, and anti‐inflammatory properties .…”