Nuclear Membrane-Targeted Gold Nanoparticles Inhibit Cancer Cell Migration and Invasion

• Published in: ACS nano 2017-04, Vol.11 (4), p.3716-3726
• Main Authors: Ali, Moustafa R. K, Wu, Yue, Ghosh, Deepraj, Do, Brian H, Chen, Kuangcai, Dawson, Michelle R, Fang, Ning, Sulchek, Todd A, El-Sayed, Mostafa A
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Apoptosis - drug effects; Cell Movement - drug effects; Cell Nucleus - drug effects; Cell Nucleus - metabolism; Drug Screening Assays, Antitumor; Female; Gold - chemistry; Gold - pharmacology; Humans; Metal Nanoparticles - chemistry; Microscopy, Atomic Force; Ovarian Neoplasms - drug therapy; Ovarian Neoplasms - pathology; Particle Size; Tumor Cells, Cultured
• ISSN: 1936-0851; 1936-086X
• DOI: 10.1021/acsnano.6b08345

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.