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Nanomaterials 2018, 8, 681 10 of 25 retinal cells, and could be experimentally applied for retinal imaging in a mouse animal model [229,230]. The bactericidal effects related to AgNP-containing nanomaterials are essential aspects which must be further considered for their exploitation as an improved class of antibacterial agent for ocular applications [14,231,232]. AgNPs can be successfully used as novel nanostructured platforms for diagnostics and the treatment of different cancers [233]. The broad-spectrum bioactivity of AgNPs makes them promising agents not only for anti-infective fighting strategies, but also in critical tumor and multi-drug resistance Nanomaterials 2018, 8, 681 10 of 24 tackling approaches. 9. Toxicity of Silver Nanoparticles Even ififAgANgPNsPpsospsoessetsrsemterenmdoeunsdaoduvsanatdavgaensttahgaetsretchoamtmrencodmthmemendfortnhoevmel afonrd cnhoavlleelngaindg cbhioalmleendgiicnaglabpiopmliecadtiicoanlsa,ptphleiicratioxnics,ittyhebierctaomxieciatynbinecteanmseivaenstiuntdeynsiuvbejesctutdoynlsyurbejeccetnotlnyl.yTrheecednatliyly. Tamheodunaitlyofasmilvoeurndteorfivseidlvferromdenriavteudraflrsoomurnceastuinraflosooduarcnedswinatfeoroidngaensdtewdabtyerhuinmgaenstseids abpyphrouxmimanasteilsy a0p.4p–r3o0xμimga[t2e3l4y].0T.4h–e3a0vμaigla[b2l3e4s]t.uTdhies apvearifloarbmledstwuditihesrepseprefcotrtmoetdhewtoitxhicrefsfpecetcst etxohitbhietetdoxbiyc AefgfNecPts ewxihthibiintebdioblyogAicgaNlPsysswteimthsi,nsbuicohloagsicbaalcstyesrtieamasn,dsuvcihruassesbaocrtehruiamaanndcveilrlus,serespoorrhtucomnatnracdeilcltso,ryepaonrdt cvoanritoraudsircetsouryltsa[n2d35,v2a3r6i]o.uAsgrNePsuslatsre[g2e3n5e,2r3a6ll]y. pArgesNePnstedaraesgheignhelryalelfyfepctrievseenantetdimaicsrohbiigahllaygenfftescwtiivteh annotnim-toicxriocbeifaflecatgsetnotshewailthynomna-mtomxicaleiaffnecteslltso[2h3e7a]l.thHyomwaevmemr, avlaiarnioucesllisn [v2i3tr7o].sHtuodwieesvdere,mvoanrisotruasteind vitro studies demonstrated the nanosilver-related toxic effects in rat hepatocytes and neuronal cells the nanosilver-related toxic effects in rat hepatocytes and neuronal cells [238], murine stem cells, [a2n3d8]h,ummuarinnelusntgemepcitehllesl,iaalncdellhsu[m23a9n].lTuhnegteopxitchiteyliaolfcAegllNsP[2s3w9]a.sTahlesotoinxviceistytigoafteAdgdNuPrsinwgainsvailvso investigated during in vivo assays. The toxicity studies performed in a rat ear model proved that assays. The toxicity studies performed in a rat ear model proved that AgNP exposure resulted AingNsigPneifixpcaonsturmeirtoescuhlotnedrinalsdigynsiffuicnacntitomn iatoncdhosunbdsreiaqludeynstfutenmctpionraaryndorsupbesremquanenentttehmeaproinragryloossr, permanent hearing loss, depending on the inoculation dose. Even low concentrations of AgNPs depending on the inoculation dose. Even low concentrations of AgNPs were absorbed by retinal cells were absorbed by retinal cells and resulted in important structural disruption, due to the increased and resulted in important structural disruption, due to the increased number of cells that underwent number of cells that underwent oxidative stress [240]. oxidative stress [240]. The possible toxicity mechanisms related to AgNPs are depicted in Figure 2 [241]. The The possible toxicity mechanisms related to AgNPs are depicted in Figure 2 [241]. The performed performed studies also proved that variations in surface charge resulting from the surface studies also proved that variations in surface charge resulting from the surface functionalization of functionalization of AgNPs can impact cellular uptake, translocation to various tissues, and AgNPs can impact cellular uptake, translocation to various tissues, and cytotoxicity. The magnitude of cytotoxicity. The magnitude of the surface charge, as measured by the zeta potential, can influence the surface charge, as measured by the zeta potential, can influence the amount of nanoparticles and the amount of nanoparticles and their mechanism of uptake into cells [242]. their mechanism of uptake into cells [242]. Figure 2. Schematiic representation of plausible methods of cellular uptake of AgNPs [243]. Reprinted with permission from [243]. Elsevier, 2015. In order to investigate the toxic effects caused by exposure to nanosilver-based systems, thorough assays are required, considering both cellular and animal models. Regarding the in vivo biocompatibility and biodistribution assays, the reported data evidenced that AgNPs can result in structural and physiological alteration of vital organs. For example, inhaled AgNPs may form deposits in the alveolar regions, leading to lung injuries, and may also generate significant modifications within the nervous system, and liver and kidney tissues. Intratracheal instillation ofPDF Image | Biomedical Applications of Silver Nanoparticles
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