The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development.
The genotype-dependent influence of functionalized multiwalled carbon nanotubes on fetal development.
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DOI：
10.1016/j.biomaterials.2013.10.027
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发表时间：
2014-01
期刊：
影响因子：
14
通讯作者：
Chen, Xiaoyuan
中科院分区：
文献类型：
--
作者：
Huang, Xinglu;Zhang, Fan;Sun, Xiaolian;Choi, Ki-Young;Niu, Gang;Zhang, Guofeng;Guo, Jinxia;Lee, Seulki;Chen, Xiaoyuan
在许多情况下，癌症是由基因缺陷引起的，这种缺陷是沿着代代相传的。可溶性碳纳米管（CNT）在癌症的诊断和治疗中显示出有前景的应用，然而，作为发展个性化纳米医学的先决条件，癌症易感个体与CNT暴露反应之间的潜在关系仍然知之甚少。在这里，我们报告，静脉注射多壁碳纳米管到p53（一个众所周知的癌症易感基因）杂合子怀孕小鼠可以诱导p53依赖性反应的胎儿发育。较大尺寸的多壁碳纳米管穿过血-胎盘屏障（BPB），限制胎儿的发育，并诱导脑畸形，而单壁和较小尺寸的多壁碳纳米管显示无或较少的胎儿毒性。一项分子机制研究发现，多壁碳纳米管直接触发p53依赖的细胞凋亡和细胞周期阻滞，以响应DNA损伤。基于分子机制，我们还加入了FDA批准的抗氧化剂N-乙酰半胱氨酸（NAC），以防止CNT诱导的核DNA损伤，减少脑发育异常。我们的研究结果表明，碳纳米管可能对胚胎的正常发育具有遗传背景依赖性毒性作用，并在潜在的临床应用中提供了新的见解，以防止纳米颗粒诱导的毒性。
In many cases cancer is caused by gene deficiency that is being passed along from generation to generation. Soluble carbon nanotubes (CNTs) have shown promising applications in the diagnosis and therapy of cancer, however, the potential relationship between cancer-prone individuals and response to CNT exposure as a prerequisite for development of personalized nanomedicine, is still poorly understood. Here we report that intravenous injections of multi-walled carbon nanotubes into p53 (a well-known cancer susceptible gene) heterozygous pregnant mice can induce p53- dependent responses in fetal development. Larger sized multi-walled carbon nanotubes moved across the blood-placenta barrier (BPB), restricted the development of fetuses, and induced brain deformity, whereas single-walled and smaller sized multi-walled carbon nanotubes showed no or less fetotoxicity. A molecular mechanism study found that multi-walled carbon nanotubes directly triggered p53-dependent apoptosis and cell cycle arrest in response to DNA damage. Based on the molecular mechanism, we also incorporated N-acetylcysteine (NAC), a FDA approved antioxidant, to prevent CNTs induced nuclear DNA damage and reduce brain development abnormalities. Our findings suggest that CNTs might have genetic background-dependent toxic effect on the normal development of the embryo, and provide new insights into protection against nanoparticle-induced toxicity in potential clinical applications.
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影响因子：
2.6
作者：
Ding, H;Wu, XL;Nagy, A
通讯作者：
Nagy, A
DOI：
10.1016/0165-3806(93)90031-5
发表时间：
1993-10-15
期刊：
DEVELOPMENTAL BRAIN RESEARCH
影响因子：
--
作者：
BAUER, HC;BAUER, H;STEINER, M
通讯作者：
STEINER, M
影响因子：
2.6
作者：
Kubota, Y;Takahashi, S;Yoshida, K
通讯作者：
Yoshida, K
碳纳米管薄膜生物传感器，用于敏感和可重复的整个病毒检测。
影响因子：
12.4
作者：
Mandal HS;Su Z;Ward A;Tang XS
通讯作者：
Tang XS
影响因子：
64.8
作者：
Green, Douglas R.;Kroemer, Guido
通讯作者：
Kroemer, Guido