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

Overview

Journal ACS Nano

Publisher American Chemical Society

Specialty Biotechnology

Date 2017 Mar 24

PMID 28333438

Citations 41

Authors

Moustafa R K Ali

Yue Wu

Deepraj Ghosh

Brian H Do

Kuangcai Chen

Michelle R Dawson

Ning Fang

Todd A Sulchek

Mostafa A El-Sayed

Affiliations

Soon will be listed here.

Abstract

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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References

Dahl K, Ribeiro A, Lammerding J . Nuclear shape, mechanics, and mechanotransduction. Circ Res. 2008; 102(11):1307-18. PMC: 2717705. DOI: 10.1161/CIRCRESAHA.108.173989. View

Ali H, Ali M, Wu Y, Selim S, Abdelaal H, Nasr E . Gold Nanorods as Drug Delivery Vehicles for Rifampicin Greatly Improve the Efficacy of Combating Mycobacterium tuberculosis with Good Biocompatibility with the Host Cells. Bioconjug Chem. 2016; 27(10):2486-2492. DOI: 10.1021/acs.bioconjchem.6b00430. View

Cross S, Jin Y, Rao J, Gimzewski J . Nanomechanical analysis of cells from cancer patients. Nat Nanotechnol. 2008; 2(12):780-3. DOI: 10.1038/nnano.2007.388. View

Stender A, Marchuk K, Liu C, Sander S, Meyer M, Smith E . Single cell optical imaging and spectroscopy. Chem Rev. 2013; 113(4):2469-527. PMC: 3624028. DOI: 10.1021/cr300336e. View

Lee J, Hale C, Panorchan P, Khatau S, George J, Tseng Y . Nuclear lamin A/C deficiency induces defects in cell mechanics, polarization, and migration. Biophys J. 2007; 93(7):2542-52. PMC: 1965451. DOI: 10.1529/biophysj.106.102426. View

Wirtz D, Konstantopoulos K, Searson P . The physics of cancer: the role of physical interactions and mechanical forces in metastasis. Nat Rev Cancer. 2011; 11(7):512-22. PMC: 3262453. DOI: 10.1038/nrc3080. View

Arvizo R, Saha S, Wang E, Robertson J, Bhattacharya R, Mukherjee P . Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle. Proc Natl Acad Sci U S A. 2013; 110(17):6700-5. PMC: 3637766. DOI: 10.1073/pnas.1214547110. View

Chithrani B, Ghazani A, Chan W . Determining the size and shape dependence of gold nanoparticle uptake into mammalian cells. Nano Lett. 2006; 6(4):662-8. DOI: 10.1021/nl052396o. View

Swift J, Ivanovska I, Buxboim A, Harada T, Dingal P, Pinter J . Nuclear lamin-A scales with tissue stiffness and enhances matrix-directed differentiation. Science. 2013; 341(6149):1240104. PMC: 3976548. DOI: 10.1126/science.1240104. View

10.

Austin L, Ahmad S, Kang B, Rommel K, Mahmoud M, Peek M . Cytotoxic effects of cytoplasmic-targeted and nuclear-targeted gold and silver nanoparticles in HSC-3 cells--a mechanistic study. Toxicol In Vitro. 2014; 29(4):694-705. DOI: 10.1016/j.tiv.2014.11.003. View

11.

Kong L, Schafer G, Bu H, Zhang Y, Zhang Y, Klocker H . Lamin A/C protein is overexpressed in tissue-invading prostate cancer and promotes prostate cancer cell growth, migration and invasion through the PI3K/AKT/PTEN pathway. Carcinogenesis. 2012; 33(4):751-9. DOI: 10.1093/carcin/bgs022. View

12.

Lautscham L, Kammerer C, Lange J, Kolb T, Mark C, Schilling A . Migration in Confined 3D Environments Is Determined by a Combination of Adhesiveness, Nuclear Volume, Contractility, and Cell Stiffness. Biophys J. 2015; 109(5):900-13. PMC: 4564685. DOI: 10.1016/j.bpj.2015.07.025. View

13.

Peer D, Karp J, Hong S, Farokhzad O, Margalit R, Langer R . Nanocarriers as an emerging platform for cancer therapy. Nat Nanotechnol. 2008; 2(12):751-60. DOI: 10.1038/nnano.2007.387. View

14.

Ge Y, Bruno M, Wallace K, Winnik W, Prasad R . Proteome profiling reveals potential toxicity and detoxification pathways following exposure of BEAS-2B cells to engineered nanoparticle titanium dioxide. Proteomics. 2011; 11(12):2406-22. DOI: 10.1002/pmic.201000741. View

15.

Ali M, Ibrahim I, Ali H, Selim S, El-Sayed M . Treatment of natural mammary gland tumors in canines and felines using gold nanorods-assisted plasmonic photothermal therapy to induce tumor apoptosis. Int J Nanomedicine. 2016; 11:4849-4863. PMC: 5036785. DOI: 10.2147/IJN.S109470. View

16.

Berk J, Tifft K, Wilson K . The nuclear envelope LEM-domain protein emerin. Nucleus. 2013; 4(4):298-314. PMC: 3810338. DOI: 10.4161/nucl.25751. View

17.

Mackey M, Ali M, Austin L, Near R, El-Sayed M . The most effective gold nanorod size for plasmonic photothermal therapy: theory and in vitro experiments. J Phys Chem B. 2014; 118(5):1319-26. PMC: 3983380. DOI: 10.1021/jp409298f. View

18.

McGregor A, Hsia C, Lammerding J . Squish and squeeze-the nucleus as a physical barrier during migration in confined environments. Curr Opin Cell Biol. 2016; 40:32-40. PMC: 4887392. DOI: 10.1016/j.ceb.2016.01.011. View

19.

Yang J, Phan H, Vaidya S, Murphy C . Nanovacuums: nanoparticle uptake and differential cellular migration on a carpet of nanoparticles. Nano Lett. 2013; 13(5):2295-302. DOI: 10.1021/nl400972r. View

20.

Bao G, Suresh S . Cell and molecular mechanics of biological materials. Nat Mater. 2003; 2(11):715-25. DOI: 10.1038/nmat1001. View