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在心脏特异性表达肿瘤坏死因子-α的转基因小鼠衰竭心脏中金纳米棒的积累。

Accumulation of gold nano-rods in the failing heart of transgenic mice with the cardiac-specific expression of TNF-α.

作者信息

Higuchi Yoshihiro, Niidome Takuro, Miyamoto Yuji, Komohara Yoshihiro, Tokunou Tomotake, Kubota Toru, Horiuchi Takahiko

机构信息

Department of Internal Medicine, Kyushu University Beppu Hospital, 4546 Tsurumihara, Beppu, Oita, 874-0838, Japan.

Department of Applied Chemistry and Biochemistry, Faculty of Advanced Science and Technology, Kumamoto University, Kumamoto, Japan.

出版信息

Heart Vessels. 2019 Mar;34(3):538-544. doi: 10.1007/s00380-018-1241-2. Epub 2018 Aug 29.

Abstract

Gold nano-rods, rod-shaped gold nanoparticles, act as contrast agents for in vivo bioimaging, drug delivery vehicles and thermal converters for photothermal therapy. Pro-inflammatory cytokines play critical roles in the development of heart failure. We examined the delivery of GNRs into the failing heart of a transgenic (TG) mouse model of inflammatory cardiomyopathy with the cardiac-specific overexpression of TNF-α. We modified GNRs with polyethylene glycol (PEG) to avoid cytotoxicity and reduce the rapid clearance of nanoparticles from blood. PEG-modified GNRs (4.5 mM as gold atoms, 200 μL) were administered intravenously to TG (n = 7) and wild-type (WT) mice (n = 5). These were killed 24 h later, and the heart, lung, liver, kidney and spleen were excised. A quantitative analysis of gold was performed using inductively coupled plasma mass or optical emission spectrometry. The amount of gold (ng) in the TG heart (3.24 ± 1.56 ng/mg heart weight) was significantly greater than that in the WT heart (1.01 ± 0.19; p < 0.05). No significant differences were observed among the other organs of TG and WT mice. The amount of gold in the TG heart was significantly and positively correlated with the ratio of the ventricular weight to body weight, which is known to be an index of ventricular hypertrophy. In conclusion, PEG-modified GNRs accumulated in the inflammatory TG heart in proportion with the severity of ventricular hypertrophy.

摘要

金纳米棒,即棒状金纳米颗粒,可作为体内生物成像的造影剂、药物递送载体以及用于光热疗法的热转换器。促炎细胞因子在心力衰竭的发展过程中起关键作用。我们研究了将金纳米棒递送至炎症性心肌病转基因(TG)小鼠模型的衰竭心脏中,该模型心脏特异性过表达肿瘤坏死因子-α。我们用聚乙二醇(PEG)修饰金纳米棒以避免细胞毒性并减少纳米颗粒从血液中的快速清除。将PEG修饰的金纳米棒(金原子浓度为4.5 mM,200 μL)静脉注射给TG小鼠(n = 7)和野生型(WT)小鼠(n = 5)。24小时后将这些小鼠处死,并切除心脏、肺、肝、肾和脾脏。使用电感耦合等离子体质谱或光发射光谱法对金进行定量分析。TG小鼠心脏中的金含量(3.24±1.56 ng/mg心脏重量)显著高于WT小鼠心脏中的金含量(1.01±0.19;p<0.05)。在TG和WT小鼠的其他器官之间未观察到显著差异。TG小鼠心脏中的金含量与心室重量与体重之比呈显著正相关,已知该比值是心室肥大的一个指标。总之,PEG修饰的金纳米棒在炎症性TG小鼠心脏中的积累与心室肥大的严重程度成正比。

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