Nanoparticle-cell interactions induced apoptosis: a case study with nanoconjugated epidermal growth factor.
Nanoparticle-cell interactions induced apoptosis: a case study with nanoconjugated epidermal growth factor.
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DOI：
10.1039/c8nr01106k
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发表时间：
2018-04-05
期刊：
影响因子：
6.7
通讯作者：
Reinhard BM
中科院分区：
文献类型：
--
作者：
Khanehzar A ;Fraire JC ;Xi M ;Feizpour A ;Xu F ;Wu L ;Coronado EA ;Reinhard BM
除了与纳米颗粒（NP）及其配体的化学组成相关的固有毒性外，生物功能化NP还可以通过NP-细胞相互作用扰乱特定的细胞过程并诱导程序性细胞死亡（细胞凋亡）。在表皮生长因子（EGF）的情况下，纳米缀合已显示出增强配体的凋亡功效，但潜在机制的关键方面及其对NP形态的依赖性仍不清楚。在该手稿中，我们表征了纳米缀合的EGF的凋亡功效作为NP尺寸（具有在20-80 nm范围内的球体直径）、纵横比（A.R.，在4.5至8.6的范围内），以及在EGFR过表达的MDA-MB-468细胞中的EGF表面负载。我们证明了一个显着的大小和形态的依赖性，在这个相对狭窄的参数空间与球形NP直径约。80 nm的纳米颗粒在诱导细胞凋亡方面比具有相当EGF负载的较小球形NP或杆状NP有效得多。发现纳米缀合的EGF触发细胞质活性氧（ROS）水平的EGFR依赖性增加，但在细胞凋亡诱导的早期时间点没有检测到线粒体ROS水平增加或线粒体膜损伤的迹象。细胞质ROS的增加伴随着细胞内谷胱甘肽稳态的扰动，这代表了NP-EGF介导的细胞凋亡的重要检查点。通过EGFR抑制剂AG 1478抑制EGFR信号传导或添加抗氧化剂N-乙酰半胱氨酸（NAC）或tempol（但不是trolox）来消除氧化应激，成功地抑制了纳米缀合的EGF的凋亡作用。一个模型来解释所观察到的EGF纳米结合增强细胞凋亡的形态依赖性和潜在的NP-细胞相互作用进行了讨论。
In addition to the intrinsic toxicity associated with the chemical composition of nanoparticles (NP) and their ligands, biofunctionalized NP can perturb specific cellular processes through NP-cell interactions and induce programmed cell death (apoptosis). In the case of the epidermal growth factor (EGF), nanoconjugation has been shown to enhance the apoptotic efficacy of the ligand, but critical aspects of the underlying mechanism and its dependence on the NP morphology remain unclear. In this manuscript we characterize the apoptotic efficacy of nanoconjugated EGF as function of NP size (with sphere diameters in the range 20–80 nm), aspect ratio (A.R., in the range of 4.5 to 8.6), and EGF surface loading in EGFR overexpressing MDA-MB-468 cells. We demonstrate a significant size- and morphology-dependence in this relatively narrow parameter space with spherical NP with a diameter of approx. 80 nm being much more efficient in inducing apoptosis than smaller spherical NP or rod-shaped NP with comparable EGF loading. The nanoconjugated EGF is found to trigger an EGFR-dependent increase in cytoplasmic reactive oxygen species (ROS) levels but no indications of increased mitochondrial ROS levels or mitochondrial membrane damage are detected at early time points of the apoptosis induction. The increase in cytoplasmic ROS is accompanied by a perturbation of the intracellular glutathione homeostasis, which represents an important check-point for NP-EGF mediated apoptosis. Abrogation of the oxidative stress through inhibition of EGFR signaling through the EGFR inhibitor AG1478 or addition of antioxidants N-acetyl cysteine (NAC) or tempol, but not trolox, successfully suppressed the apoptotic effect of nanoconjugated EGF. A model to account for the observed morphology dependence of EGF nanoconjugation enhanced apoptosis and the underlying NP-cell interactions is discussed.
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DOI：
10.1016/j.bbamcr.2012.06.019
发表时间：
2012-10
影响因子：
5.1
作者：
Circu, Magdalena L.;Aw, Tak Yee
通讯作者：
Aw, Tak Yee
影响因子：
10.8
作者：
Huang, Changjin;Zhang, Yao;Zhang, Sulin
通讯作者：
Zhang, Sulin
影响因子：
4.8
作者：
Couet, J;Sargiacomo, M;Lisanti, MP
通讯作者：
Lisanti, MP
影响因子：
16.6
作者：
Hartmann, Raimo;Weidenbach, Marcel;Parak, Wolfgang J.
通讯作者：
Parak, Wolfgang J.
影响因子：
5.6
作者：
Ceresa BP
通讯作者：
Ceresa BP