Nuclear Membrane-Targeted Gold Nanoparticles Inhibit Cancer Cell Migration and Invasion.
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.
Laser Dynamics Lab (LDL), School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
Moustafa R K
0000-0002-2027-1006
MRK
Ali
Laser Dynamics Lab (LDL), School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
Yue
0000-0001-7680-9285
Y
Wu
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University , Providence, Rhode Island 02912, United States.
Deepraj
D
Ghosh
School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
Brian H
BH
Do
Department of Chemistry, Georgia State University , P.O. Box 3965, Atlanta, Georgia 30302, United States.
Kuangcai
K
Chen
Department of Molecular Pharmacology, Physiology and Biotechnology, Brown University , Providence, Rhode Island 02912, United States.
Michelle R
MR
Dawson
Department of Chemistry, Georgia State University , P.O. Box 3965, Atlanta, Georgia 30302, United States.
Ning
0000-0003-4710-0984
N
Fang
School of Mechanical Engineering, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
Todd A
0000-0003-4196-6293
TA
Sulchek
Laser Dynamics Lab (LDL), School of Chemistry and Biochemistry, Georgia Institute of Technology , Atlanta, Georgia 30332-0400, United States.
Mostafa A
0000-0002-7674-8424
MA
El-Sayed
D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D002467:Cell Nucleus / Q000187:drug effects* / Q000378:metabolism; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006046:Gold / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D053768:Metal Nanoparticles / Q000737:chemistry*; D018625:Microscopy, Atomic Force; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000473:pathology; D010316:Particle Size; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D006046:Gold
AFM; cancer cell migration and invasion; gold nanoparticles; lamin A/C; metastasis; nuclear stiffness; three-dimensional DIC microscopy