Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration

Short- and long-term distribution and toxicity of gold nanoparticles in the rat after a single-dose intravenous administration
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DOI:
10.1016/j.nano.2014.06.005
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发表时间:
2014-11-01
影响因子:
5.4
通讯作者:
Carmo, Helena
Carmo, Helena
中科院分区:
医学2区
文献类型:
--
作者:
Fraga, Sonia;Brandao, Ana;Carmo, Helena

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表面化学对金纳米颗粒(AuNPs)的稳定性和生物相容性起着重要作用,这对其临床应用至关重要。我们评估了类似于20 nm柠檬酸和五肽CALNN包被的AuNPs在大鼠一次静脉注射后的短期(30分钟)和长期(28天)的生物分布和毒性。Cit和CALNN-AuNPs注射大鼠的AuNPs分布模式在所评估的时间点非常相似。这两种AuNPs都被迅速从血液中移除,并优先在肝脏中积聚。在第28天,肝脏仍然是主要的蓄积部位,但与30min时相比,水平明显降低。在给予CALNN-AuNPs的大鼠中,观察到脾萎缩和血液学结果与轻度贫血相一致。在我们的实验条件下,表面涂层对AuNPs的毒性影响比对其生物分布的影响更大。需要改进封闭肽的设计,以提高多肽包裹的AuNPs的生物医学适用性。来自临床编辑:研究了类似于20 nm柠檬酸和五肽CALNN包裹的金纳米颗粒在大鼠单次静脉注射后的生物分布和毒性。注射后30分钟,肝脏迅速清除和蓄积,28天后出现轻度贫血和脾萎缩。作者还得出结论,这种毒性与覆盖蛋白有关,而不是与颗粒的生物分布有关,为未来金纳米颗粒的设计提供了重要的建议。(C)2014 Elsevier Inc.保留所有权利。
Surface chemistry plays an important role in gold nanoparticles (AuNPs) stability and biocompatibility, which are crucial for their implementation into the clinical setting. We evaluated short- (30 min) and long-term (28 days) biodistribution and toxicity of similar to 20 nm citrate-and pentapeptide CALNN-coated AuNPs after a single intravenous injection in rats. The pattern of AuNPs distribution in Cit- and CALNN-AuNPs-injected rats was very similar in the assessed time-points. Both AuNPs were quickly removed from the bloodstream and preferentially accumulated in the liver. At 28 days liver remained the main accumulation site but at significantly lower levels compared to those found at 30 min. Spleen atrophy and hematological findings compatible with mild anemia were observed in CALNN-AuNPs-administered rats. Under our experimental conditions, surface coating had more impact on toxicity rather than on biodistribution of the AuNPs. Improvements in the design of capping peptides need to be done to increase biomedical applicability of peptide-coated AuNPs.From the Clinical Editor: The biodistribution and toxicity of similar to 20 nm citrate-and pentapeptide CALNN-coated gold nanoparticles was investigated after a single intravenous injection in rats. Rapid clearance and hepatic accumulation was found at 30-minutes, whereas mild anemia and spleen atrophy was seen 28 days post injection. The authors also concluded that the toxicity was related to the capping proteins as opposed to the biodistribution of the particles, providing important suggestion for future design of gold nanoparticles. (C) 2014 Elsevier Inc. All rights reserved.