1. Molecular Imaging & Therapy Branch, Division of Convergence Technology, National Cancer Center, 111 Jungbalsan-ro, Ilsandong-gu, Goyang, Gyeonggi-do 410-769, Republic of Korea;
2. Department of Chemistry, Institute of Nanosensor and Biotechnology, Dankook University, 126 Jukjeon-dong, Yongin-si, Gyeonggi-do 448-701, Republic of Korea;
Theranostics. 2013 Dec 1;4(1):1-11. doi: 10.7150/thno.7101. eCollection 2013.
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.
由氯（Ce6）-透明质酸（HA）缀合物制备的巨噬细胞靶向治疗性纳米粒子（MacTNP）具有光学性质，可被巨噬细胞中的活性氧（ROS）激活。MacTNP 在其天然状态下是非荧光和非光毒性的。然而，当用 ROS 处理时，特别是用过氧亚硝酸盐处理时，它们会变得高度荧光和光毒性。体外细胞研究表明，MacTNP 在激活的巨噬细胞内发射近红外（NIR）荧光。NIR 荧光在细胞外环境中被猝灭。在没有光照的情况下，MacTNP 在巨噬细胞中达到 10 μM 的 Ce6 浓度时是无毒的。然而，MacTNP 在光照下以光剂量依赖性方式变得光毒性。特别是，与人类真皮成纤维细胞和非激活的巨噬细胞相比，在激活的巨噬细胞中观察到明显更高的光毒性作用。具有高靶背比的 ROS 响应性 MacTNP 可能在动脉粥样硬化的选择性近红外荧光成像和随后的光动力治疗中具有显著的潜力，副作用最小。
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