Abstract 21489: Magnetite Nanoparticles for both Magnetic Hyperthermia and 3T MRI of Macrophages
Introduction: Macrophages are important targets for imaging and treating vascular inflammation. Magnetite nanoparticles (MN) have both hyperthermia and MRI properties. We compared MNs for hyperthermic destruction of macrophages and for in vivo imaging of experimental vascular inflammation on a whole-body 3T MRI system.
Methods: Two types of MN were studied — one with a neutral liposomal membrane (ML, 94 nm), the other with a cationic liposomal membrane (MCL, 150 nm). Magnetic hyperthermia of macrophages (RAW, 1x106) was performed by incubation with ML or MCL (20 μg/mL) for 4 hours, followed by exposure to an alternating magnetic field for 30 minutes. 3T MRI was performed on FVB mice (n=9). A macrophage-rich carotid artery lesion was induced by ligation after high-fat diet for one month and diabetes induction by streptozotocin. MRI was performed 2 weeks after ligation, with mice injected intravenously with ML (n=4) or MCL (n=5) and then imaged at 48 hours on a whole-body 3T MRI scanner (Signa HDx, GE Healthcare) using a gradient echo sequence. MN accumulation was assessed by measuring the extent of T2*-induced reduction in carotid lumen size. Histological analysis was performed to assess accumulation of MN in vascular macrophages.
Results: Magnetic hyperthermia of macrophages induced 79.6% cell death with MCL, but only 10.9% with ML. In vivo MRI showed that both ML and MCL caused significant and similar T2*-induced reduction in lumen size of ligated left carotid arteries compared to non-ligated right carotid controls (p<0.02 for both vs. controls, p=0.8 for ML vs. MCL; Figs. A, B). Prussian blue and Mac-3 staining demonstrated MN in neointimal macrophages (Fig. C).
Conclusions: Neutral liposomal MN show superior macrophage hyperthermia and can also image vascular macrophages in vivo by whole-body 3T MRI. MN are promising agents for both detecting and treating vascular inflammation.
- © 2010 by American Heart Association, Inc.