Hisanori Kosuge1, Maki Nakamura2, Ayako Oyane2, Kazuko Tajiri3, Nobuyuki Murakoshi3, Satoshi Sakai3, Akira Sato3, Atsushi Taninaka4, Taishiro Chikamori5, Hidemi Shigekawa4, Kazutaka Aonuma3. 1. Department of Cardiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, 160-0023, Tokyo, Japan. hkosuge@tokyo-med.ac.jp. 2. Nanomaterials Research Institute, National Institute of Advanced Industrial Science and Technology (AIST), Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki, 305-8565, Japan. 3. Department of Cardiology, Faculty of Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki, 305-8575, Japan. 4. Faculty of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Ibaraki, 305-8573, Tsukuba, Japan. 5. Department of Cardiology, Tokyo Medical University, 6-7-1 Nishishinjuku, Shinjuku-ku, 160-0023, Tokyo, Japan.
Abstract
PURPOSE: Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT. PROCEDURES: Mouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs. RESULTS: The CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 μg/ml or 200 μg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001). CONCLUSIONS: Macrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.
PURPOSE: Macrophages contribute to the progression of vascular inflammation, making them useful targets for imaging and treatment of vascular diseases. Gold nanoparticles (GNPs) are useful as computed tomography (CT) contrast agents and light absorbers in photothermal therapy. In this study, we aimed to assess the viability of macrophages incubated with GNPs after near-infrared (NIR) laser light exposure and to evaluate the utility of intravenously injected GNPs for in vivo imaging of vascular inflammation in mice using micro-CT. PROCEDURES: Mouse macrophage cells (RAW 264.7) were incubated with GNPs and assessed for GNP cellular uptake and cell viability before and after exposure to NIR laser light. For in vivo imaging, macrophage-rich atherosclerotic lesions were induced by carotid ligation in hyperlipidemic and diabetic FVB mice (n = 9). Abdominal aortic aneurysms (AAAs) were created by angiotensin II infusion in ApoE-deficient mice (n = 9). These mice were scanned with a micro-CT imaging system before and after the intravenous injection of GNPs. RESULTS: The CT attenuation values of macrophages incubated with GNPs were significantly higher than those of cells incubated without GNPs (p < 0.04). Macrophages incubated with and without GNPs showed similar viability. The viability of macrophages incubated with GNPs (100 μg/ml or 200 μg/ml) was decreased by high-intensity NIR laser exposure but not by low-intensity NIR laser exposure. In vivo CT images showed higher CT attenuation values in diseased carotid arteries than in non-diseased contralateral arteries, although the difference was not statistically significant. The CT attenuation values of the perivascular area in AAAs of mice injected with GNPs were significantly higher than those of mice without injection (p = 0.0001). CONCLUSIONS: Macrophages with GNPs had reduced viability upon NIR laser exposure. GNPs intravenously injected into mice accumulated in sites of vascular inflammation, allowing detection of carotid atherosclerosis and AAAs in CT imaging. Thus, GNPs have potential as multifunctional biologically compatible particles for the detection and therapy of vascular inflammation.
Authors: Peter Chhour; Johoon Kim; Barbara Benardo; Alfredo Tovar; Shaameen Mian; Harold I Litt; Victor A Ferrari; David P Cormode Journal: Bioconjug Chem Date: 2016-11-18 Impact factor: 4.774
Authors: Jin Hyung Lee; Sarah P Sherlock; Masahiro Terashima; Hisanori Kosuge; Yoriyasu Suzuki; Andrew Goodwin; Joshua Robinson; Won Seok Seo; Zhuang Liu; Richard Luong; Michael V McConnell; Dwight G Nishimura; Hongjie Dai Journal: Magn Reson Med Date: 2009-12 Impact factor: 4.668
Authors: Ketan B Ghaghada; Pingping Ren; Laxman Devkota; Zbigniew Starosolski; Chen Zhang; Deborah Vela; Igor V Stupin; Eric A Tanifum; Ananth V Annapragada; Ying H Shen; Scott A LeMaire Journal: Arterioscler Thromb Vasc Biol Date: 2021-02-04 Impact factor: 8.311