Ag nanoparticles sensitize IR-induced killing of cancer cells
Ag nanoparticles sensitize IR-induced killing of cancer cells
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银纳米粒子使红外线诱导的癌细胞杀伤变得敏感
DOI：
10.1038/cr.2009.89
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发表时间：
2009-08
期刊：
影响因子：
44.1
通讯作者：
Liu, Jiwei
中科院分区：
文献类型：
--
作者：
Ma, Jun;Huang, Lan;Fan, Xu;Gu, Jiayu;Zhang, Yu;Chen, Xi;Gu, Ning;Guo, Zhirui;Wang, Changling;Xu, Ruizhi;Chen, Zhongping;Wang, Meng;Jiang, Xiaoli;Sun, Xinchen;Li, Yang;Liu, Jiwei
结合更好的癌症诊断与治疗效果的纳米颗粒系统正在设计的基础上合并的纳米技术与细胞和分子技术。这些纳米级载体的表面通常用生物分子官能化以用于稳定和靶向递送。纳米核和相关功能分子的组合可以穿过细胞膜[1]，纳米材料的表面（包括涂层和相关功能分子）在决定其与细胞相互作用的结果方面起着关键作用[2，3]。研究纳米材料在生物系统中的潜在影响通常需要将纳米颗粒施用到细胞培养系统或体内活生物体中。然而，应该注意的是，在这种条件下，已知纳米颗粒会从生物系统中吸附蛋白质，由此产生的表面蛋白质的异质性可能反过来影响纳米材料的生物效应[4，5]。为了最大限度地减少这种非特异性影响，在这项研究中，我们用来自胎牛血清（FBS）的蛋白质修饰了纳米材料的表面，FBS是一种通常用于细胞培养的补充剂。有趣的是，我们最近发现，对于硅烷包被的单分散磁铁矿纳米颗粒（MNP），FBS的额外表面改性似乎有助于癌细胞对颗粒的摄取。许多先前的研究已经检查了在常规细胞培养条件下纳米颗粒被吸收到细胞中后引起的细胞毒性[6-8]。然而，细胞内纳米颗粒的性质及其在更复杂的情况下对细胞过程的影响，例如当细胞用电离辐射（IR）处理时，在很大程度上仍然不清楚。最近，据报道，某些金纳米颗粒（用聚乙二醇（PEG）和氨基酸包覆）可以增强小鼠结肠直肠腺癌和乳腺癌细胞中辐射诱导的细胞毒性[9，10]。然而，一直缺乏系统的分析，不同的纳米材料通常如何影响细胞的辐射敏感性，以及纳米粒子及其涂层的各自贡献。为了解决这个问题，我们在本研究中检查了三种不同的纳米材料，磁铁矿、金和银纳米颗粒，它们具有不同的表面涂层（对于磁铁矿颗粒）或不同的尺寸范围（对于金和银颗粒）（补充信息，图S1），以确定它们对放射诱导的胶质瘤细胞杀伤的潜在影响（实验详情见补充信息，数据S1）。我们选择胶质瘤细胞作为模型系统，因为大多数胶质母细胞瘤（GBM）对IR治疗不敏感甚至耐药，这也反映在已建立的胶质瘤细胞系中。因此，增强IR诱导的胶质瘤细胞杀伤效应可能为GBM患者提供治疗益处。（补充信息，图S2），并用以下四种表面分子之一涂覆它们：内消旋-2，3-二巯基琥珀酸（DMSA），和带有各种官能团的硅烷，所述官能团包括氨基（NH 2），短链PEG，和羧基（COOH）（图1A）。我们还制备了直径为10、20和40 nm的金纳米颗粒（AuNP）和直径为20、50和100 nm的银纳米颗粒（AgNP）（图1A）。所有颗粒均用FBS改性，然后进行辐射介导的灭菌（详情和补充信息见方法，图S3、S4）。然后，我们研究了这些制备的纳米颗粒对三种不同胶质瘤细胞系（即C6（起源于...
Nanosized particulate systems combining better cancer diagnosis with therapeutic effect are being designed based on the merging of nanotechnology with cellular and molecular techniques. The surface of these nanoscale carriers is often functionalized with biological molecules for stabilization and targeted delivery. The combinations of nano-core and associated functional molecules can cross the cell membrane [1], and the surface of nanomaterials (including coating and associated functional molecules) plays a critical role in determining the outcome of their interactions with cells [2, 3]. Studying the potential effects of nanomaterials in biological systems often requires the administration of nanoparticles into a cell culture system or into living organisms in vivo. It should be noted, however, that under such conditions nanopaticles are known to adsorb proteins from the biological system, and the resulting heterogeneity in surface proteins may in turn affect the biological effects of nanomaterials [4, 5]. To minimize such non-specific effect, in this study we have modified the surface of our nanomaterials with proteins from fetal bovine serum (FBS), a supplement normally used for cell culture. Interestingly, we have recently found that for silane-coated monodisperse magnetite nanoparticles (MNPs), additional surface modification by FBS appears to facilitate particle uptake by cancer cells. A number of previous studies have examined cytotoxicity elicited by nanoparticles after their uptake into cells under regular cell culture conditions [6-8]. However, the property of intracellular nanoparticles and their effect on cellular processes under more complex scenarios such as when cells are treated with ionizing radiation (IR) remain largely unclear. Recently, it was reported that certain gold nanoparticles (coated with polyethylene glycol (PEG) and amino acids) could enhance radiationinduced cytotoxicity in mice colorectal adenocarcinoma and breast cancer cells [9, 10]. However, there has been a lack of systematic analyses on how different nanomaterials generally affect cellular radiation sensitivity, as well as the respective contributions by nanoparticles and their coatings. To address this issue, we have examined in this study three different nanomaterials, magnetite, gold and silver nanoparticles, with either distinct surface coatings (for magnetite paticles) or distinct size ranges (for gold and silver particles)(Supplementary information, Figure S1), for their potential effects on radiation-induced killing of glioma cells (experimental details in Supplementary information, Data S1). We chose glioma cells as a model system because most of glioblastoma multiform (GBM) is insensitive or even resistant to IR therapy, which is also reflected in the established glioma cell lines. Thus, enhancing the effect of IR-induced killing of glioma cells may offer therapeutic benefit for patients with GBM.We prepared 12-nm monodisperse MNPs (Supplementary information, Figure S2), and coated them with one of the following four surface molecules: meso-2, 3-dimercaptosuccinic acid (DMSA), and silanes bearing various functional groups including amino group (NH2), short-chain PEG, and carboxylic group (COOH)(Figure 1A). We also prepared gold nanoparticles (AuNPs) of diameter 10, 20 and 40 nm, and silver nanoparticles (AgNPs) of diameter 20, 50 and 100 nm (Figure 1A). All the particles were modified with FBS followed by radiation-mediated sterilization (see Methods for details and Supplementary information, Figure S3, S4). We then examined the effects of these prepared nanoparticles on cell survival and cell radiation sensitivity in three different glioma cell lines, namely C6 (originated …
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影响因子：
14
作者：
Chung, Yi-Chang;Chen, I-Han;Chen, Ching-Jung
通讯作者：
Chen, Ching-Jung
影响因子：
13.3
作者：
Kong, Tao;Zeng, Jie;Xing, James Z.
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Xing, James Z.
影响因子：
38.3
作者：
Jiang, Wen;Kim, Betty Y. S.;Chan, Warren C. W.
通讯作者：
Chan, Warren C. W.
影响因子：
3.5
作者：
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通讯作者：
M. Alvarez;J. Friend;L. Yeo
影响因子：
17.1
作者：
AshaRani, P. V.;Mun, Grace Low Kah;Valiyaveettil, Suresh
通讯作者：
Valiyaveettil, Suresh