Fast detection of liver fibrosis with collagen-binding single-nanometer iron oxide nanoparticles via T 1 -weighted MRI

SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a -weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity co...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2023-05, Vol.120 (18), p.e2220036120
Main Authors: Zhang, Juanye, Ning, Yingying, Zhu, Hua, Rotile, Nicholas J, Wei, He, Diyabalanage, Himashinie, Hansen, Eric C, Zhou, Iris Y, Barrett, Stephen C, Sojoodi, Mozhdeh, Tanabe, Kenneth K, Humblet, Valerie, Jasanoff, Alan, Caravan, Peter, Bawendi, Moungi G
Format: Article
Language:English
Subjects:
Animals
Collagen - analysis
Contrast Media - chemistry
Disease Models, Animal
Liver - pathology
Liver Cirrhosis - pathology
Magnetic Iron Oxide Nanoparticles
Magnetic Resonance Imaging - methods
Magnetite Nanoparticles
Mice
Nanoparticles
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Summary:SNIO-CBP, a single-nanometer iron oxide (SNIO) nanoparticle functionalized with a type I collagen-binding peptide (CBP), was developed as a -weighted MRI contrast agent with only endogenous elements for fast and noninvasive detection of liver fibrosis. SNIO-CBP exhibits 6.7-fold higher relaxivity compared to a molecular gadolinium-based collagen-binding contrast agent CM-101 on a per CBP basis at 4.7 T. Unlike most iron oxide nanoparticles, SNIO-CBP exhibits fast elimination from the bloodstream with a 5.7 min half-life, high renal clearance, and low, transient liver enhancement in healthy mice. We show that a dose of SNIO-CBP that is 2.5-fold lower than that for CM-101 has comparable imaging efficacy in rapid (within 15 min following intravenous injection) detection of hepatotoxin-induced liver fibrosis using -weighted MRI in a carbon tetrachloride-induced mouse liver injury model. We further demonstrate the applicability of SNIO-CBP in detecting liver fibrosis in choline-deficient -amino acid-defined high-fat diet mouse model of nonalcoholic steatohepatitis. These results provide a platform with potential for the development of high relaxivity, gadolinium-free molecular MRI probes for characterizing chronic liver disease.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.2220036120