ROS-responsive activatable photosensitizing agent for imaging and photodynamic therapy of activated macrophages.
ROS-responsive activatable photosensitizing agent for imaging and photodynamic therapy of activated macrophages.
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作者：
Kim H;Kim Y;Kim IH;Kim K;Choi Y
由四氯乙烯(Ce6)-透明质酸(HA)偶联物制备的巨噬细胞靶向治疗纳米粒(MacTNP)的光学性质可以被巨噬细胞中的活性氧自由基(ROS)激活。MacTNP在其天然状态下是非荧光和无光毒性的。然而，当用ROS，特别是过氧亚硝酸盐处理时，它们会变得高度荧光和光毒。体外细胞研究表明，MacTNP在激活的巨噬细胞内发出近红外(NIR)荧光。近红外荧光在胞外环境中被猝灭。在没有光线的情况下，当Ce6浓度达到10μM时，MacTNP对巨噬细胞无毒。然而，MacTNP在光照下以光剂量依赖的方式变得光毒。特别是，与人皮肤成纤维细胞和未激活的巨噬细胞相比，激活的巨噬细胞的光毒作用明显更强。ROS反应的MacTNP具有很高的靶本底比，在选择性近红外荧光成像和随后的光动力学治疗动脉粥样硬化方面有很大的潜力，副作用最小。
The optical properties of macrophage-targeted theranostic nanoparticles (MacTNP) prepared from a Chlorin e6 (Ce6)-hyaluronic acid (HA) conjugate can be activated by reactive oxygen species (ROS) in macrophage cells. MacTNP are nonfluorescent and nonphototoxic in their native state. However, when treated with ROS, especially peroxynitrite, they become highly fluorescent and phototoxic. In vitro cell studies show that MacTNP emit near-infrared (NIR) fluorescence inside activated macrophages. The NIR fluorescence is quenched in the extracellular environment. MacTNP are nontoxic in macrophages up to a Ce6 concentration of 10 μM in the absence of light. However, MacTNP become phototoxic upon illumination in a light dose-dependent manner. In particular, significantly higher phototoxic effect is observed in the activated macrophage cells compared to human dermal fibroblasts and non-activated macrophages. The ROS-responsive MacTNP, with their high target-to-background ratio, may have a significant potential in selective NIR fluorescence imaging and in subsequent photodynamic therapy of atherosclerosis with minimum side effects.
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