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Theranostics 2020, Vol. 10, Issue 20 suppressing A TP production. Besides, ROS induced by AgNPs may ultimately lead to DNA damage [255]. Superoxide radicals directed to mitochondria may enhance mitochondrial outer membrane permeabilization (MOMP) and the release of Cyt c, destroy the electron transport chain, and impair mitochondrial function [256]. Some factors influence the generation of ROS induced by AgNPs. Smaller size and higher concentration of AgNPs exhibit higher induction of ROS and stronger cytotoxicity, and sharp increased ROS appear in different cancer cells treated with AgNPs [220]. DNA Damage AgNPs can induce ROS production to disrupt DNA structure, or directly contact with DNA to cause DNA mutations [209, 241, 248]. High levels of ROS can generate damage to DNA double helix in a concentration-dependent manner, including breaking 9012 the single or double-stranded DNA, affecting base modifications and DNA cross-links [241, 253, 257]. AgNPs-treated cancer cells may exhibit DNA methylation, DNA base pairing errors, DNA repair defects and increased chromosomal aberrations [209, 248, 258]. AgNPs may play an important role in the regulation of gene expression of cells. AgNPs inhibit the proliferation of cells and trigger DNA repair defects by down-regulating the functions of proteins involved in cell cycle progression and DNA repair [259]. For example, proliferating cell nuclear antigen (PCNA) gene plays an important role in DNA synthesis and repair as a cofactor for DNA polymerase. PCNA is down-regulated in AgNPs- exposed cells. While the up-regulation of the apoptotic precursor protein Bax suggests that AgNPs initiate apoptosis via the mitochondrial pathway [260]. AgNPs-treated cells may undergo S phase, G2/M phase and sub-G1 cell cycle arrests in a Figure 4. A schematic diagram of anticancer mechanisms of AgNPs. AgNPs can destroy the ultrastructure of cancer cell, induce ROS generation and DNA damage, promote apoptosis and autophagy by regulating multiple signaling pathways. http://www.thno.orgPDF Image | Silver nanoparticles Synthesis medical applications safety
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