Abstract
The ability to determine the severity of renal fibrosis, which is involved in most chronic kidney diseases, may be beneficial for monitoring disease progression and management. The aim of this study was to assess a new method involving gold nanoparticles conjugated to an anti-collagen-I antibody (Co-I-AuNPs) as a computed tomography (CT) imaging contrast for the evaluation of renal fibrosis in situ. Gold nanoparticles conjugated to an anti-collagen-I antibody were prepared using gold chloride reduction with sodium citrate and coated with polyethylene glycol (PEG), and their size was determined by electron microscopy and nanoparticle tracking analysis. Anti-collagen-I antibody was then conjugated to PEG-SH/COOH on the AuNP surface. The success of antibody conjugation was tested in vitro using collagen-coated plate and mouse stenotic kidney sections and in vivo using micro-CT and multidetector CT imaging. Bare AuNPs were 18.7 ± 0.6 nm and PEG-coated AuNPs were 45.3 ± 0.1 nm in size. In vitro, Co-I-AuNPs specifically bound to both a collagen-coated plate and mouse fibrotic kidneys. Furthermore, the stenotic mouse kidney showed increased Co-I-AuNPs retention compared with the contralateral kidney (59.3 ± 5.1 vs 45.1 ± 1.7 HU, P = 0.05), which correlated with its collagen deposition. Micro-CT also detected gold signals in situ in the Co-I-AuNP-injected kidney, which colocalized with histological trichrome staining. Gold nanoparticles conjugated to an anti-collagen-I antibody are able to visualize kidney fibrosis in vitro and in situ and may be useful for nondestructive quantification of tissue fibrosis.
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