Michael J Lipinski1, M Teresa Albelda2, Juan C Frias3, Stasia A Anderson4, Dror Luger5, Peter C Westman5, Ricardo O Escarcega5, David G Hellinga5, Ron Waksman5, Andrew E Arai4, Stephen E Epstein5. 1. MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC, USA. Electronic address: mjlipinski12@gmail.com. 2. GIBI2(30), Grupo de Investigación Biomédica en Imagen, IIS La Fe, Valencia, Spain. 3. Departamento de Ciencias Biomédicas, Universidad CEU Cardenal Herrera, Valencia, Spain. 4. Advanced Cardiovascular Imaging Laboratory, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA. 5. MedStar Heart and Vascular Institute, MedStar Washington Hospital Center, Washington, DC, USA.
Abstract
INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murine myocardial infarction model. METHODS: Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.
INTRODUCTION: Nanoparticles may serve as a promising means to deliver novel therapeutics to the myocardium following myocardial infarction. We sought to determine whether lipid-based liposomal nanoparticles can be shown through different imaging modalities to specifically target injured myocardium following intravenous injection in an ischemia-reperfusion murinemyocardial infarction model. METHODS:Mice underwent ischemia-reperfusion surgery and then either received tail-vein injection with gadolinium- and fluorescent-labeled liposomes or no injection (control). The hearts were harvested 24h later and underwent T1 and T2-weighted ex vivo imaging using a 7 Tesla Bruker magnet. The hearts were then sectioned for immunohistochemistry and optical fluorescent imaging. RESULTS: The mean size of the liposomes was 100nm. T1-weighted signal intensity was significantly increased in the ischemic vs. the non-ischemic myocardium for mice that received liposomes compared with control. Optical imaging demonstrated significant fluorescence within the infarct area for the liposome group compared with control (163±31% vs. 13±14%, p=0.001) and fluorescent microscopy confirmed the presence of liposomes within the ischemic myocardium. CONCLUSIONS: Liposomes traffic to the heart and preferentially home to regions of myocardial injury, enabling improved diagnosis of myocardial injury and could serve as a vehicle for drug delivery.
Authors: I M Dauber; K M VanBenthuysen; I F McMurtry; G S Wheeler; E J Lesnefsky; L D Horwitz; J V Weil Journal: Circ Res Date: 1990-04 Impact factor: 17.367
Authors: Tal Dvir; Michael Bauer; Avi Schroeder; Jonathan H Tsui; Daniel G Anderson; Robert Langer; Ronglih Liao; Daniel S Kohane Journal: Nano Lett Date: 2011-09-14 Impact factor: 11.189
Authors: David E Sosnovik; Elisabeth Garanger; Elena Aikawa; Matthias Nahrendorf; Jose-Luiz Figuiredo; Guangping Dai; Fred Reynolds; Anthony Rosenzweig; Ralph Weissleder; Lee Josephson Journal: Circ Cardiovasc Imaging Date: 2009-09-29 Impact factor: 7.792
Authors: Robert C Scott; Jenna M Rosano; Zhanna Ivanov; Bin Wang; Parkson Lee-Gau Chong; Andrew C Issekutz; Deborah L Crabbe; Mohammad F Kiani Journal: FASEB J Date: 2009-06-17 Impact factor: 5.191
Authors: Philip M Robson; Damini Dey; David E Newby; Daniel Berman; Debiao Li; Zahi A Fayad; Marc R Dweck Journal: JACC Cardiovasc Imaging Date: 2017-10