In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice.

In vivo study of spherical gold nanoparticles: inflammatory effects and distribution in mice.
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DOI:
10.1371/journal.pone.0058208
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Valenzuela SM
Valenzuela SM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Chen H;Dorrigan A;Saad S;Hare DJ;Cortie MB;Valenzuela SM

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21 nm的金纳米颗粒(AuNPs)在体外已经被很好地表征为通过主动摄取来靶向巨噬细胞的能力。然而,这种AuNPs对生理系统的短期影响,特别是体内脂肪组织中驻留的巨噬细胞,在很大程度上是未知的。本项目研究了小鼠暴露于AuNPs后脂肪组织中炎性细胞因子的分布、器官毒性和变化。将雄性C57BL/6小鼠单次腹腔注射(7.85μg AuNPs/g)。每天记录体重和能量摄入量。分别于注射后1小时、24小时和72小时取材进行脏器毒性试验。用电子显微镜观察AUNP的分布。用实时荧光定量聚合酶链式反应检测腹壁脂肪垫内促炎细胞因子的表达和巨噬细胞的数量。在注射AuNP后72小时,发现对照组和AuNP处理组小鼠的每日能量摄入量和体重相似。然而,在AuNP处理的小鼠中,脂肪质量明显较小。注射IP后,AuNPs在腹部脂肪组织中迅速积聚,部分在肝脏中可见。注射AUNP后1h至72h,脂肪组织中肿瘤坏死因子α和IL-6mRNA水平均下降,巨噬细胞数无明显变化。对重要器官(肝脏和肾脏)没有可检测到的毒性。我们的21 nm球形AuNPs对小鼠没有可测量的器官或细胞毒性,但与显著的脂肪损失和抑制炎症作用有关。随着肥胖和肥胖相关疾病的发病率不断上升,我们的发现为金纳米颗粒作为治疗此类疾病的治疗剂的潜在开发提供了新的途径。
Gold nanoparticles (AuNPs) of 21 nm have been previously well characterized in vitro for their capacity to target macrophages via active uptake. However, the short-term impact of such AuNPs on physiological systems, in particular resident macrophages located in fat tissue in vivo, is largely unknown. This project investigated the distribution, organ toxicity and changes in inflammatory cytokines within the adipose tissue after mice were exposed to AuNPs. Male C57BL/6 mice were injected intraperitoneally (IP) with a single dose of AuNPs (7.85 μg AuNPs/g). Body weight and energy intake were recorded daily. Tissues were collected at 1 h, 24 h and 72 h post-injection to test for organ toxicity. AuNP distribution was examined using electron microscopy. Proinflammatory cytokine expression and macrophage number within the abdominal fat pad were determined using real-time PCR. At 72 hours post AuNP injection, daily energy intake and body weight were found to be similar between Control and AuNP treated mice. However, fat mass was significantly smaller in AuNP-treated mice. Following IP injection, AuNPs rapidly accumulated within the abdominal fat tissue and some were seen in the liver. A reduction in TNFα and IL-6 mRNA levels in the fat were observed from 1 h to 72 h post AuNP injection, with no observable changes in macrophage number. There was no detectable toxicity to vital organs (liver and kidney). Our 21 nm spherical AuNPs caused no measurable organ or cell toxicity in mice, but were correlated with significant fat loss and inhibition of inflammatory effects. With the growing incidence of obesity and obesity-related diseases, our findings offer a new avenue for the potential development of gold nanoparticles as a therapeutic agent in the treatment of such disorders.
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DOI: 10.1126/science.7678183
发表时间: 1993-01-01
期刊: SCIENCE
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