Abstract 1189: Imaging and Photodynamic Therapy of Atherosclerotic Plaque Using a Macrophage-Targeted Nanoparticle
Background: Photodynamic therapy (PDT) of atherosclerotic plaque macrophages may be a promising approach to stabilize rupture-prone lesions. Here we investigated a macrophage-targeted photosensitizing nanoparticle (CLIO-AF750-THPC) to image and treat inflamed atheroma in vivo.
Methods: CLIO-AF750-THPC is a dextran-based nanoparticle that contains a near-infrared (NIR) fluorochrome (AF750, ex/em 749/775 nm) for optical imaging and a photosensitizer (THPC, abs 648 nm) for PDT. PDT efficacy of CLIO-AF750-THPC was first tested in vitro in murine macrophages and compared to an untargeted photosensitizer (chlorin e6) using the MTS assay for cell viability. Next, apoE−/− mice (n=15) were intravenously injected with CLIO-AF750-THPC or CLIO-AF750 control (10 mg Fe/kg). After 24 hours, carotid arterial plaques were imaged with intravital fluorescence microscopy (IVFM) in the AF750 channel, and then treated with PDT (650 nm laser, 3 min, 11 J/cm2). After 3 weeks, mice underwent repeated IVFM. Mice were sacrificed at 1 day and 3 weeks post-PDT for histopathology.
Results: In vitro PDT with macrophage-targeted CLIO-AF750-THPC was 8x more efficient at cell killing (LC50=100 nM) compared to chlorin e6. On IVFM, CLIO-AF750-THPC was localized in inflamed carotid plaques, and was confirmed to be macrophage localized on fluorescence microscopy. One day post PDT, CLIO-AF750-THPC mice showed extensive macrophage apoptosis in atheroma that was not present in the CLIO-AF750 controls. After 3 weeks, total plaque NIR fluorescence in controls (reflecting macrophage content) increased by 13.4-fold (p<.05). In contrast, the total plaque NIR fluorescence in the CLIO-AF750-THPC group was only mildly increased (1.7×). Plaques from the CLIO-AF750-THPC PDT group demonstrated fewer foam cells compared to plaques in the control CLIO-AF750 group.
Conclusions: CLIO-AF750-THPC is a multifunctional nanoparticle that allows optical imaging and targeted PDT of macrophage-rich atherosclerotic lesions. CLIO-AF750-THPC based PDT results in fewer plaque foam cells consistent with a plaque stabilization effect.