Nanoparticles can cause DNA damage across a cellular barrier
Nanoparticles can cause DNA damage across a cellular barrier
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DOI：
10.1038/nnano.2009.313
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发表时间：
2009-12-01
影响因子：
38.3
通讯作者：
Case, Charles Patrick
中科院分区：
文献类型：
--
作者：
Bhabra, Gevdeep;Sood, Aman;Case, Charles Patrick
纳米颗粒在医学上的使用越来越多，这引起了人们对它们进入人体特权部位的能力的担忧。在这里，我们展示了钴铬纳米颗粒（直径29.5 +/- 6.3 nm）可以穿过完整的细胞屏障破坏人类成纤维细胞，而无需穿过屏障。这种损伤是由一种新机制介导的，这种新机制涉及嘌呤核苷酸（如ATP）的传递，以及通过连接蛋白间隙连接或半通道和泛连接蛋白通道在屏障内传递细胞间信号。结果，包括DNA损伤而没有显著的细胞死亡，与直接暴露于纳米颗粒的细胞观察到的结果不同。我们的研究结果表明，在评估纳米颗粒的安全性时，间接效应的重要性。当使用纳米颗粒靶向病变状态时，需要考虑细胞屏障后组织的潜在损伤。
The increasing use of nanoparticles in medicine has raised concerns over their ability to gain access to privileged sites in the body. Here, we show that cobalt-chromium nanoparticles (29.5 +/- 6.3 nm in diameter) can damage human fibroblast cells across an intact cellular barrier without having to cross the barrier. The damage is mediated by a novel mechanism involving transmission of purine nucleotides (such as ATP) and intercellular signalling within the barrier through connexin gap junctions or hemichannels and pannexin channels. The outcome, which includes DNA damage without significant cell death, is different from that observed in cells subjected to direct exposure to nanoparticles. Our results suggest the importance of indirect effects when evaluating the safety of nanoparticles. The potential damage to tissues located behind cellular barriers needs to be considered when using nanoparticles for targeting diseased states.