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Wei et al. Page 8 Application in hepatocellular carcinoma—An in vitro cytotoxic study conducted by Kim et al. [22] demonstrated that the cytotoxicity of AgNPs against human liver HepG2 cells is primarily the result of oxidative stress. Recently, Sahu et al. [67] revealed a significant concentration-dependent cytotoxicity of AgNPs in HepG2 cells and that a different mechanism of AgNPs-induced mitochondrial injury leads to the cytotoxicity. Notably, Faedmaleki et al. [68] showed that AgNPs had a 44-times stronger inhibitory effect on HepG2 cells compared with normal cells (primary liver cells of mice). Application in lung cancer—AgNPs have also been shown to display cytotoxicity to lung cancer cells. Foldbjerg et al. [69] observed a dose-dependent reduction in mitochondrial function of human alveolar cell line A549 cells. It was shown that AgNPs are taken up by the cells, leading to increased production of ROS and ultimately apoptotic and necrotic cell death. Moreover, Nazir et al. [70] showed that AgNPs have effective anticancer properties against the H157 (squamous cell lung carcinoma) cell line with an IC50 of 3.6μM. Application in skin and/or oral carcinoma—Work by the Nazir group showed that AgNPs have effective anticancer properties with an IC50 of 0.36μM against HT144 melanoma cell lines [70]. Recently, Austin et al. [71] demonstrated that the nuclear- targeting peptide-conjugated AgNPs cause DNA double-strand (ds) breaks and a subsequent increase in the sub-G1 (apoptotic) population in the HSC-3 cancer cell model at lower concentrations compared with nuclear-targeting gold nanoparticles (AuNPs). Concluding remarks and future perspectives In summary, silver nanoparticles exhibit particularly unique physical, chemical, optical, and biological properties that different from other biomedical nanomaterials and, thus, can serve as therapeutic platforms in many biomedical applications, including but not limited to: (i) antiviral agents; (ii) photosensitizers and/or radiosensitizers; and (iii) anticancer therapeutic agents in leukemia, breast cancer, hepatocellular carcinoma, lung carcinoma, and skin and/or oral carcinoma. However, despite their promising potential in medical applications, the impact of AgNPs on human health (both positive and negative) needs to be fully understood before their wider use. The successful translation of silver nanotechnology to the clinic requires the development of simple, safe, cost-effective, and eco-friendly preparations of AgNPs, and a fuller understanding of the safety control mechanisms as well as the biodistribution and pharmacokinetics of AgNPs in clinical applications. Acknowledgments This work was supported by funds from St John’s University Research Seed Grant (No. 579-1110-7002) and the Department of Pharmaceutical Sciences to Z-S.C. References 1. Habouti S, et al. Synthesis of silver nano-fir-twigs and application to single molecules detection. J Mater Chem. 2010; 20:5215–5219. 2. Hu XH, Chan CT. Photonic crystals with silver nanowires as a near-infrared superlens. Appl Phys Lett. 2004; 85:1520–1522. Drug Discov Today. Author manuscript; available in PMC 2016 May 01. Author Manuscript Author Manuscript Author Manuscript Author ManuscriptPDF Image | Silver nanoparticles: synthesis, properties, therapeutic apps
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