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Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by 19F NMR of VCAM-1 targeted nanobeacons

2009; Elsevier BV; Volume: 5; Issue: 3 Linguagem: Inglês

10.1016/j.nano.2008.12.002

1549-9642

Richard Southworth, Megan M. Kaneda, Junjie Chen, Lei Zhang, Huiying Zhang, Xiaoxia Yang, Reza Razavi, Gregory M. Lanza, Samuel A. Wickline,

Advanced MRI Techniques and Applications

We have designed multifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1), which is up-regulated in numerous inflammatory processes. These perfluorocarbon-cored nanoparticles emit a unique 19F magnetic resonance (MR) signature, providing the potential to localize and quantify VCAM-1 expression in early atherosclerosis. Nanoparticle-VCAM-1 targeting specificity was confirmed by in vitro binding and competition studies. ApoE-null and control C57-BL6 mice (n = 6/group), fed a Western diet for 35 weeks, were injected i.v. with targeted or non-targeted nanoparticles. After two hours, kidneys were excised and prepared for analysis. ApoE-null kidneys exhibited increased VCAM-1-targeted nanoparticle content over healthy controls by 19F MR spectroscopy (36.5+8.8 vs. 9.3+2.2 × 108/g, P < .05), which correlated with increased VCAM-1 staining (2.5 ± 1.3% vs. 0.9 ± 0.3%, P < .05); their relative biodistributions were confirmed by fluorescence microscopy and MR imaging. These molecular imaging agents offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising 19F MR spectroscopy and imaging. Multifunctional nanoparticulate reporter bioprobes capable of targeting vascular cell adhesion molecule 1 (VCAM-1) are reported in this paper. These perfluorocarbon-cored nanoparticles offer new approaches for detection, quantification, and longitudinal evaluation of early inflammation utilising 19F MR spectroscopy and imaging.