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

TY - JOUR

T1 - Renal vascular inflammation induced by Western diet in ApoE-null mice quantified by F-19 NMR of VCAM-1 targeted nanobeacons

AU - Southworth, Richard

AU - Kaneda, Megan

AU - Chen, Junjie

AU - Zhang, Lei

AU - Zhang, Huiying

AU - Yang, Xiaoxia

AU - Razavi, Reza

AU - Lanza, Gregory

AU - Wickline, Samuel A.

PY - 2009/9

Y1 - 2009/9

N2 - 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 F-19 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 F-19 MR spectroscopy (36.5+8.8 vs. 9.3+2.2 x 10(8)/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 F-19 MR spectroscopy and imaging.

AB - 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 F-19 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 F-19 MR spectroscopy (36.5+8.8 vs. 9.3+2.2 x 10(8)/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 F-19 MR spectroscopy and imaging.

U2 - 10.1016/j.nano.2008.12.002

DO - 10.1016/j.nano.2008.12.002

M3 - Article

VL - 5

SP - 359

EP - 367

JO - Nanomedicine-Nanotechnology Biology And Medicine

JF - Nanomedicine-Nanotechnology Biology And Medicine

IS - 3

ER -