Abstract 16171: Carbon Nanotubes Enable Optical Ablation of Vascular Macrophages
Introduction: Macrophages are important targets for detection and therapy of atherosclerosis. Carbon nanotubes (NT) have imaging and therapeutic properties, as they can heat/ablate cells through optical excitation. We have shown NT are taken up by vascular macrophages. We evaluated NT for optical ablation of macrophages, both in vitro and in murine carotid arteries.
Methods: In vitro: mouse macrophage cells were incubated for 24 hours with or without NT (concentration: 100 nM). Ten million cells in each group was exposed to continuous 808 nm laser source (RPMC Lasers, Inc., O'Fallon, MO) for 2 minutes at 5W/cm2, followed by incubation of cells for 24 hours. Cell viability was assessed by MTT assay. Carotids: FVB mice (N=15) had a macrophage-rich carotid atherosclerotic lesion created through high fat diet and diabetes induction, followed 2 weeks later by ligation of the left carotid artery. After 2 weeks, mice were injected with or without NT (concentration: 0.6 μ M) via tail vein. At 48 post-injection, the ligated left carotid arteries were excised and immediately exposed ex vivo to the same laser for 5 minutes at 5W/cm2 (N=11) or no laser exposure (N=4). After ablation, the sections of carotid arteries with or without NT were stained with anti-caspase-3 antibody.
Results: Optical excitation in vitro of macrophages incubated with NT caused visual disruption of the cell pellet (Fig 1A) but no change in the NT-free cells, with >80% reduction in viable cells (Fig 1B). Optical excitation ex vivo of NT+ carotid arteries resulted in apoptosis of neointimal macrophages (N=6, Fig 2A), but no significant apoptosis in NT- carotids (N=5, Fig 2B) and NT+ carotids without laser. Quantitative analysis showed significantly higher caspase-positive cells in NT+ carotids post-laser (Fig 2C, p=0.045 vs. NT-).
Conclusions: Optical excitation of NTs causes macrophage ablation in vitro and in murine carotid arteries and is a promising approach for targeted nanotherapy of vascular inflammation.
- © 2011 by American Heart Association, Inc.