Nuclear Membrane-Targeted Gold Nanoparticles Inhibit Cancer Cell Migration and Invasion.
Nuclear Membrane-Targeted Gold Nanoparticles Inhibit Cancer Cell Migration and Invasion.
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DOI：
10.1021/acsnano.6b08345
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发表时间：
2017-04-25
期刊：
影响因子：
17.1
通讯作者：
El-Sayed MA
中科院分区：
文献类型：
--
作者：
Ali MRK;Wu Y;Ghosh D;Do BH;Chen K;Dawson MR;Fang N;Sulchek TA;El-Sayed MA
大多数癌症患者死于转移。最近的研究表明，金纳米颗粒（AuNPs）可以减缓癌细胞的迁移/侵袭速度并抑制转移。由于细胞的核硬度很大程度上降低了细胞迁移，我们的假设是，将 AuNP 靶向细胞核区域可以增强核硬度，从而抑制细胞迁移和侵袭。我们的结果表明，与非靶向 AuNP 相比，AuNP 核靶向后，卵巢癌细胞的活力显着降低。此外，使用原子力显微镜，我们观察到细胞核硬度增强。为了了解癌细胞迁移/侵袭抑制的机制，使用高分辨率三维成像显微镜清晰地成像了靶向AuNPs的确切位置，这表明AuNPs被捕获在核膜上。此外，我们观察到核纤层蛋白 A/C 蛋白的表达水平大大增加，该蛋白位于内核膜中，作为核纤层的结构成分，增强核硬度。我们提出，被捕获在核膜上的 AuNPs 不仅（1）增加了细胞核的机械刚度，而且（2）刺激了核膜周围核纤层蛋白 A/C 的过度表达，从而增加了核刚度并减缓了癌细胞的迁移和侵袭。
Most cancer patients die from metastasis. Recent studies have shown that gold nanoparticles (AuNPs) can slow down the migration/invasion speed of cancer cells and suppress metastasis. Since nuclear stiffness of the cell largely decreases cell migration, our hypothesis is that targeting AuNPs to the cell nucleus region could enhance nuclear stiffness, and therefore inhibit cell migration and invasion. Our results showed that upon nuclear targeting of AuNPs, the ovarian cancer cell motilities decrease significantly, compared with nontargeted AuNPs. Furthermore, using atomic force microscopy, we observed an enhanced cell nuclear stiffness. In order to understand the mechanism of cancer cell migration/invasion inhibition, the exact locations of the targeted AuNPs were clearly imaged using a high-resolution three-dimensional imaging microscope, which showed that the AuNPs were trapped at the nuclear membrane. In addition, we observed a greatly increased expression level of lamin A/C protein, which is located in the inner nuclear membrane and functions as a structural component of the nuclear lamina to enhance nuclear stiffness. We propose that the AuNPs that are trapped at the nuclear membrane both (1) add to the mechanical stiffness of the nucleus and (2) stimulate the overexpression of lamin A/C located around the nuclear membrane, thus increasing nuclear stiffness and slowing cancer cell migration and invasion.
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