Photosensitive fluorescent dye contributes to phototoxicity and inflammatory responses of dye-doped silica NPs in cells and mice.
Photosensitive fluorescent dye contributes to phototoxicity and inflammatory responses of dye-doped silica NPs in cells and mice.
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作者：
Zhao Y;Ye Y;Zhou X;Chen J;Jin Y;Hanson A;Zhao JX;Wu M
染料掺杂的荧光二氧化硅纳米颗粒提供高强度和光稳定的荧光信号。然而，一些掺杂染料分子是光敏的。选择一种广泛使用的光敏荧光掺杂剂红宝石，系统地研究了染料掺杂二氧化硅纳米颗粒（NPs）的光毒性。我们研究了细胞活力，DNA损伤和活性氧（ROS）水平在肺泡巨噬细胞使用染料掺杂NPs辐照或不辐照。我们的研究结果表明，红宝石掺杂二氧化硅NPs可以诱导大量的ROS、DNA损伤、凋亡和MH-S细胞增殖受损。小鼠体内研究表明，红宝石掺杂二氧化硅NPs诱导了显著的炎症细胞因子产生，降低了ERK1/2和NF-κB等信号蛋白的表达，并增加了髓过氧化物酶和脂质过氧化测定的肺损伤。引人注目的是，我们还发现，与肝脏和肺部相比，单独的红宝石和NPs都能诱导肾脏的系统性信号激活，而肝脏和肺部表现出高度选择性的信号模式，这比红宝石掺杂的二氧化硅NPs更为明显。此外，我们发现了二氧化硅nps诱导的应激和毒性的关键生物标志物（例如HMGB1），并证明了不同器官中差异调节的反应模式。我们的研究结果首次表明，与裸NPs相比，红宝石掺杂二氧化硅NPs对动物靶细胞的炎症反应更少，但热疗效果更强，并且具有时间和剂量依赖性。
Dye-doped fluorescent silica nanoparticles provide highly intense and photostable fluorescence signals. However, some dopant dye molecules are photosensitive. A widely-used photosensitive fluorescent dopant, RuBpy, was chosen to systematically investigate the phototoxicity of the dye-doped silica nanoparticles (NPs). We investigated cell viability, DNA damage, and Reactive Oxygen Species (ROS) levels in alveolar macrophages using the dye-doped NPs with or without irradiation. Our results showed that the RuBpy-doped silica NPs could induce significant amount of ROS, DNA damage, apoptosis and impaired proliferation in MH-S cells. In vivo studies in mice showed that RuBpy-doped silica NPs induced significant inflammatory cytokine production and lowered expression in signaling proteins such as ERK1/2 and NF-κB as well as increased lung injury determined by myeloperoxidase and lipid peroxidation. Strikingly, we also found that both RuBpy alone and NPs induced systemic signaling activation in the kidney compared to the liver and lung where showed highly selective signaling patterns, which is more pronounced than RuBpy-doped silica NPs. Moreover, we discovered a critical biomarker (e.g., HMGB1) for silica NPs-induced stress and toxicity and demonstrated differentially-regulated response patterns in various organs. Our results indicate for the first time that the RuBpy-doped silica NPs may impose less inflammatory responses but stronger thermotherapeutic effects on target cells in animals than naked NPs in a time- and dose-dependent manner.
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影响因子：
17.1
作者：
Kumar R;Roy I;Ohulchanskky TY;Vathy LA;Bergey EJ;Sajjad M;Prasad PN
通讯作者：
Prasad PN
影响因子：
4.1
作者：
Jin, Yuhui;Kannan, Shibichakravarthy;Zhao, Julia Xiaojun
通讯作者：
Zhao, Julia Xiaojun
影响因子：
3.2
作者：
Berg, J. Michael;Romoser, Amelia A.;Sayes, Christie M.
通讯作者：
Sayes, Christie M.
影响因子：
5.4
作者：
Li, Xuefeng;Zhou, Xikun;Ye, Yan;Li, Yi;Li, Jiaxin;Privratsky, Breanna;Wu, Erxi;Gao, Hongwei;Huang, Canhua;Wu, Min
通讯作者：
Wu, Min
影响因子：
15
作者：
Lee, Jung Heon;Wang, Zidong;Liu, Juewen;Lu, Yi
通讯作者：
Lu, Yi