Autophagy induction by silver nanowires: A new aspect in the biocompatibility assessment of nanocomposite thin films

• Published in: Toxicology and applied pharmacology 2012-11, Vol.264 (3), p.451-461
• Main Authors: Verma, Navin K., Conroy, Jennifer, Lyons, Philip E., Coleman, Jonathan, O'Sullivan, Mary P., Kornfeld, Hardy, Kelleher, Dermot, Volkov, Yuri
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; ATOMIC FORCE MICROSCOPY; Autophagy; Autophagy - drug effects; Biocompatible Materials - chemistry; Biocompatible Materials - toxicity; Biohazard assessment; Biological and medical sciences; Blotting, Western; Cell Line; Chemical and industrial products toxicology. Toxic occupational diseases; Cytotoxicity; DOSES; ENVIRONMENTAL EXPOSURE; HEALTH HAZARDS; HOMEOSTASIS; Humans; IMPEDANCE; Medical sciences; Metals and various inorganic compounds; Mice; Microscopy, Electron, Transmission; Nanocomposites - chemistry; Nanocomposites - toxicity; Nanowires - chemistry; Nanowires - toxicity; QUANTUM WIRES; SILVER; Silver - chemistry; Silver - toxicity; Silver nanowire (AgNW); THIN FILMS; TOXICITY; Toxicology; TRANSMISSION ELECTRON MICROSCOPY
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2012.08.023

Nanomaterials and their enabled products have increasingly been attracting global attention due to their unique physicochemical properties. Among these emerging products, silver nanowire (AgNW)-based thin films are being developed for their promising applications in next generation nanoelectronics and nanodevices. However, serious concerns remain about possible health and safety risks they may pose. Here, we employed a multi-modal systematic biocompatibility assessment of thin films incorporating AgNW. To represent the possible routes of nanomaterial entry during occupational or environmental exposure, we employed four different cell lines of epithelial, endothelial, gastric, and phagocytic origin. Utilizing a cell-based automated image acquisition and analysis procedure in combination with real-time impedance sensing, we observed a low level of cytotoxicity of AgNW, which was dependent on cell type, nanowire lengths, doses and incubation times. Similarly, no major cytotoxic effects were induced by AgNW-containing thin films, as detected by conventional cell viability and imaging assays. However, transmission electron microscopy and Western immunoblotting analysis revealed AgNW-induced autophasosome accumulation together with an upregulation of the autophagy marker protein LC3. Autophagy represents a crucial mechanism in maintaining cellular homeostasis, and our data for the first time demonstrate triggering of such mechanism by AgNW in human phagocytic cells. Finally, atomic force microscopy revealed significant changes in the topology of cells attaching and growing on these films as substrates. Our findings thus emphasize the necessity of comprehensive biohazard assessment of nanomaterials in modern applications and devices and a thorough analysis of risks associated with their possible contact with humans through occupational or environmental exposure. [Display omitted] ► Thin films containing nanomaterials are subject to increasing contact with humans. ► This study provides multi-modal biohazard assessment of AgNW-based thin films. ► Thin films containing AgNW affect human cell topology and attachment. ► AgNW toxicity depends on cell type, nanowire length, dose, and exposure time. ► AgNW can induce the process of autophagy in phagocytic cells.