4.7 Article

Nontoxic silver nanocluster-induced folding, fibrillation, and aggregation of blood plasma proteins

期刊

出版社

ELSEVIER SCIENCE BV
DOI: 10.1016/j.ijbiomac.2018.07.177

关键词

Silver nanocluster; Fibrillation; gamma-globulin; Insulin; Human serum albumin

资金

  1. Kermanshah University of Medical Sciences [95689]
  2. Kermanshah University of Technology
  3. Razi University Research Center

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In recent years, concerns have been raised considering the potential risks of nanocluster (NC) for the environment and human health. Since the blood circulation system is probably the first entry route of NC into the human body, adsorption of blood proteins on NC may change cellular responses, including cellular uptake efficiency, bio distribution patterns, and nanotoxicity profiles, besides other biological effects. Therefore, the interaction of NCs with proteins and the cellular implications can be therapeutically of great importance. Adsorption of human blood proteins on NCs has been methodically investigated. In the present study, the first analysis of fibrillation was conducted between MBI-AgNCs and human serum (a complex biofluid). AgNCs were prepared by coating with 2-mercaptobenzimidazole. Then, interactions with human blood proteins, such as immunoglobulin, albumin, and insulin were investigated using various experimental approaches. Upon protein association, the fluorescence of proteins significantly decreased, accompanied by a blue shift in the AgNCs-human serum albumin (HSA) system and a red shift in the AgNCs-insulin/gamma-globulin. Concomitantly, circular dichroism spectroscopy and atomic force microscopy were employed to investigate the effects of protein binding to NCs. We found that AgNCs induced gamma-globulin aggregation. HSA at the AgNC surface was partially unfolded and could promote protein self-assembly into amyloid fibrils, while the surface morphology remained unchanged after insulin incubation. The atomic force microscopy (AFM) data and the ThT and CR analysis of the proteins, as well as circular dichroism (CD) and fluorescence findings, support the use of AgNCs as an indicator for monitoring the progress of HSA fibrillogenesis. Additionally, cytotoxicity assays were used to ensure the biocompatibility of nanoparticles within the applicable limits. (C) 2018 Elsevier B.V. All rights reserved.

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