Near infrared imaging and photothermal ablation of vascular inflammation using single-walled carbon nanotubes.

Near infrared imaging and photothermal ablation of vascular inflammation using single-walled carbon nanotubes.
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DOI:
10.1161/jaha.112.002568
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发表时间:
2012-12
影响因子:
5.4
通讯作者:
McConnell MV
McConnell MV
中科院分区:
医学2区
文献类型:
--
作者:
Kosuge H;Sherlock SP;Kitagawa T;Dash R;Robinson JT;Dai H;McConnell MV

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巨噬细胞是动脉粥样硬化的关键因素。单壁碳纳米管(SWNTs)在细胞成像和热疗方面显示出良好的性能,可能会应用于血管巨噬细胞。用单壁碳纳米管(14.7nmol/L)对小鼠巨噬细胞(RAW264.7)进行体外摄取和光热破坏。单壁碳纳米管被94±6%的巨噬细胞摄取,光暴露引起93±3%的细胞死亡。然后,在诱导高脂血症和糖尿病后,观察颈动脉结扎的FVB小鼠(n=33)的血管巨噬细胞摄取和消融情况。结扎后2周行近红外荧光(NIRF)颈动脉成像(n=12),尾静脉注射SWNT-Cy5.5(8nmolCy5.5)。对新鲜切除的颈动脉(n=21)进行光热加热和巨噬细胞凋亡的检测。与假手术组相比,单壁碳纳米管的NIRF信号强度明显增强(P<0.05,结扎组和假手术组)。免疫荧光染色显示SWNT-Cy5.5和巨噬细胞在动脉粥样硬化病变中共存。光(808 Nm)照射组结扎的左颈总动脉中加入单壁碳纳米管的大鼠出现加热和巨噬细胞凋亡,而不加单壁碳纳米管或不加光照射的对照组则无此作用。碳纳米管在体内聚集在动脉粥样硬化的巨噬细胞中,为血管炎症的成像和光热治疗提供了一个多功能的平台。
Macrophages are critical contributors to atherosclerosis. Single-walled carbon nanotubes (SWNTs) show promising properties for cellular imaging and thermal therapy, which may have application to vascular macrophages. In vitro uptake and photothermal destruction of mouse macrophage cells (RAW264.7) were performed with SWNTs (14.7 nmol/L) exposed to an 808-nm light source. SWNTs were taken up by 94±6% of macrophages, and light exposure induced 93±3% cell death. In vivo vascular macrophage uptake and ablation were then investigated in carotid-ligated FVB mice (n=33) after induction of hyperlipidemia and diabetes. Two weeks postligation, near-infrared fluorescence (NIRF) carotid imaging (n=12) was performed with SWNT-Cy5.5 (8 nmol of Cy5.5) given via the tail vein. Photothermal heating and macrophage apoptosis were evaluated on freshly excised carotid arteries (n=21). NIRF of SWNTs showed higher signal intensity in ligated carotids compared with sham, confirmed by both in situ and ex vivo NIRF imaging (P<0.05, ligation versus sham). Immunofluorescence staining showed colocalization of SWNT-Cy5.5 and macrophages in atherosclerotic lesions. Light (808 nm) exposure of freshly excised carotids showed heating and induction of macrophage apoptosis in ligated left carotid arteries with SWNTs, but not in control groups without SWNTs or without light exposure. Carbon nanotubes accumulate in atherosclerotic macrophages in vivo and provide a multifunctional platform for imaging and photothermal therapy of vascular inflammation.