CuS纳米颗粒作为光热开关通过调控TRPV1离子通道以阻止动脉粥样硬化形成
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- 英文论文题名：CuS Nanoparticle as a photothermal switch for the control of TRPV1 signalling to impede atherosclerosis progression
- 论文作者：高雯 ; 孙宇慧 ; 唐波
- 英文论文作者：Wen Gao ; Yuhui Sun ; Bo Tang ; College of Chemistry ; Chemical Engineering and Materials Science ; Shandong Normal University
- 年：2016
- 作者机构：山东师范大学化学化工与材料科学学院;
- 论文关键词：动脉粥样硬化 ; TRPV1离子通道 ; CuS纳米颗粒 ; 精准调控
- 会议召开时间：2016-07-01
- 会议录名称：中国化学会第30届学术年会摘要集-第三十八分会：纳米生物效应与纳米药物化学
- 语种：中文
- 分类号：R543.5
- 学会代码：ZGHY
- 会议名称：中国化学会第30届学术年会-第三十八分会 ; 纳米生物效应与纳米药物化学
- 会议地点：中国辽宁大连
- 主办单位：中国化学会
- 学会名称：中国化学会
- 页数：1
- 文件大小：189k
- 原文格式：D
- 会议级别：全国
摘要
动脉粥样硬化是引发心脑血管疾病的首要原因。其早期症状主要表现为血管平滑肌细胞(VSMCs)内大量脂质的堆积,形成泡沫细胞。研究发现,利用辣椒素激活VSMCs膜表面TRPV1阳离子通道可以诱导其发生细胞自噬,减少脂质的积累,以阻止细胞泡沫样变。但是辣椒素具有很大的副作用,而且它对TRPV1的激活缺乏可控性。考虑到TRPV1也是一个对温度敏感的离子通道,我们利用CuS这种具有良好光热效应的纳米颗粒,在其表面修饰上能够靶向TRPV1的特异性抗体组装成Cu S-TRPV1,借助980 nm近红外激光,实现对VSMCs膜表面TRPV1的时间和空间上的可控开关。激活TRPV1,VSMCs发生Ca~(2+)内流,自噬信号通路被激活。通过诱导自噬,氧化性低密度脂蛋白造成的脂质堆积明显减少,阻止了泡沫细胞的形成。CuS-TRPV1还可作为造影剂,对病变血管部位进行了光声成像。在成像指导下,实现了对ApoE-/-小鼠体内TRPV1的精准激活,有效抑制了动脉硬化的形成。(图1)。
Atherosclerosis, an inflammatory process consisting largely of the accumulation of lipids within the artery wall, is the major cause of morbidity and mortality worldwide. Although activation of TRPV1 channels by capsaicin may reduce lipid storag, direct use of such TRPV1 agonist in clinical applications is limited by the potential side effects and the lack of temporal and spatial precisions. Here, we develop a CuS nanoparticles-based switch for photothermal activation of TRPV1 signalling to impede the progression of atherosclerosis. This switch consists of CuS NPs conjugated with TRPV1 monoclonal antibody(CuS-TRPV1) and enables specific binding to TRPV1 on the plasma membrane of VSMC. Following NIR light irradiation, the local temperature increase opened the TRPV1 channels and caused calcium ions influx and subsequent autophagy activation, which significantly reduced the accumulation of lipids and the formation of foam cells in ox LDL-treated VSMCs. Importantly, CuS-TRPV1 could provide obvious structural PA imaging of cardiovascular, making it feasible for in vivo temporally and spatially precise control of TRPV1-signalling. After 12 weeks of PA image-guided therapy, lipid storage and atherosclerotic lesions were significantly reduced in the arteries from Apo E-/-mice on a high-fat diet.
Atherosclerosis, an inflammatory process consisting largely of the accumulation of lipids within the artery wall, is the major cause of morbidity and mortality worldwide. Although activation of TRPV1 channels by capsaicin may reduce lipid storag, direct use of such TRPV1 agonist in clinical applications is limited by the potential side effects and the lack of temporal and spatial precisions. Here, we develop a CuS nanoparticles-based switch for photothermal activation of TRPV1 signalling to impede the progression of atherosclerosis. This switch consists of CuS NPs conjugated with TRPV1 monoclonal antibody(CuS-TRPV1) and enables specific binding to TRPV1 on the plasma membrane of VSMC. Following NIR light irradiation, the local temperature increase opened the TRPV1 channels and caused calcium ions influx and subsequent autophagy activation, which significantly reduced the accumulation of lipids and the formation of foam cells in ox LDL-treated VSMCs. Importantly, CuS-TRPV1 could provide obvious structural PA imaging of cardiovascular, making it feasible for in vivo temporally and spatially precise control of TRPV1-signalling. After 12 weeks of PA image-guided therapy, lipid storage and atherosclerotic lesions were significantly reduced in the arteries from Apo E-/-mice on a high-fat diet.
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