Non-Invasive Imaging Serum Amyloid A Activation through the NF-[kappa]B Signal Pathway upon Gold Nanostructure Exposure

• Published in: Small (Weinheim an der Bergstrasse, Germany) Vol. 12; no. 24; p. 3270
• Main Authors: Zhang, Yulong, Zhou, Qianqian, Yan, Shaoduo, Zhang, Ning, Zhao, Man, Ma, Cong, He, Chulin, Fu, Qiuxia, Wu, Tao, Wang, Xiaohui, Zhan, Linsheng
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley Subscription Services, Inc 01.06.2016
• Subjects: Cytokines; Nanotechnology; Rodents
• ISSN: 1613-6810; 1613-6829
• DOI: 10.1002/smll.201600019

With the objective of investigating the acute activation of inflammatory cascades upon exposure to gold nanoparticles (GNPs) as well as detailing the mechanisms, a reporter mouse model that allows for non-invasive and longitudinal imaging of hepatic acute-phase serum amyloid A (SAA) activation is constructed. The model is able to visualize SAA activation at the transcriptional stage, with higher sensitivity than serum protein detection by ELISA. GNPs of various sizes (10-80 nm) and geometries are assessed using the reporter mice with results demonstrating that 50 nm nanospheres (GNS50) possess the highest capacity to induce hepatic SAA activation. Detailed analysis uncovers that resident macrophages in the liver are the main origins of these cytokines and that the exposure to GNS50 significantly induces the M1 macrophage phenotype. Moreover, those M1-polarized macrophages, together with the subsequently secreted pro-inflammatory cytokines, exert effects on hepatocytes and then initiate SAA transcription through the NF-[kappa]B signal pathway. The results detail the sequential reactions to GNPs among macrophages, inflammatory mediators, and SAA-synthesizing hepatocytes, which shed light on the acute effects of GNPs on the body. In addition, the established in situ and highly sensitive SAA detection system is expected to have vast applications in evaluating NP-induced acute inflammatory reactions.