Back to Journals » International Journal of Nanomedicine » Volume 7

Nucleocytoplasmic transport blockage by SV40 peptide-modified gold nanoparticles induces cellular autophagy

Authors Tsai T, Hou, Wang, Yang, Yeh, Shieh, Su W

Received 18 June 2012

Accepted for publication 25 July 2012

Published 8 October 2012 Volume 2012:7 Pages 5215—5234


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 4

Tsung-Lin Tsai,1,5 Chia-Cheng Hou,1,5 Hao-Chen Wang,1,5 Zih-Syuan Yang,2 Chen-Sheng Yeh,4 Dar-Bin Shieh,2,3 Wu-Chou Su1,5

1Institute of Basic Medical Sciences, 2Institute of Oral Medicine and Department of Stomatology, 3Center for Micro/Nano Science and Technology, 4Department of Chemistry, National Cheng Kung University, Tainan, Taiwan; 5Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

Abstract: Gold nanoparticles modified with the nuclear localization signal from simian virus 40 large T antigen (GNP-PEG/SV40) accumulate on the cytoplasmic side of the nuclear membrane in HeLa cells. Accumulation of GNP-PEG/SV40 around the nucleus blocks nucleocytoplasmic transport and prevents RNA export and nuclear shuttling of signaling proteins. This long-term blockage of nucleocytoplasmic transport results in cell death. This cell death is not caused by apoptosis or necrosis because caspases 3 and 9 are not activated, and the expression of annexin V/propidium iodide is not enhanced in HeLa cells after treatment. Using transmission electron microscopy, autophagosomes and autolysosomes were seen to appear after 72 hours of treatment with GNP-PEG/SV40. Increasing levels of enhanced green fluorescent protein-microtubule-associated protein 1 light chain 3 (EGFP-LC3)-positive punctate and LC3-II confirmed GNP-PEG/SV40-induced autophagy. In SiHa cells, treatment did not induce accumulation of GNP-PEG/SV40 around the nucleus and autophagy. Treating cells with wheat germ agglutinin, a nuclear pore complex inhibitor, induced autophagy in both HeLa and SiHa cells. GNP-PEG/SV40-induced autophagy plays a role in cell death, not survival, and virus-mediated small hairpin RNA silencing of Beclin-1 attenuates cell death. Taken together, the results indicate that long-term blockade of nucleocytoplasmic transport results in autophagic cell death.

Keywords: gold nanoparticles, nucleocytoplasmic transport blockage, autophagy, wheat germ agglutinin

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]


Other article by this author:

PLGA nanoparticles codeliver paclitaxel and Stat3 siRNA to overcome cellular resistance in lung cancer cells

Su WP, Cheng FY, Shieh DB, Yeh CS, Su WC

International Journal of Nanomedicine 2012, 7:4269-4283

Published Date: 3 August 2012

Readers of this article also read:

Social representation of hearing aids: cross-cultural study in India, Iran, Portugal, and the United Kingdom

Manchaiah V, Danermark B, Vinay, Ahmadi T, Tomé D, Krishna R, Germundsson P

Clinical Interventions in Aging 2015, 10:1601-1615

Published Date: 6 October 2015

Evaluating the potential of cubosomal nanoparticles for oral delivery of amphotericin B in treating fungal infection

Yang Z, Chen M, Yang M, Chen J, Fang W, Xu P

International Journal of Nanomedicine 2014, 9:327-336

Published Date: 6 January 2014

Simple filter microchip for rapid separation of plasma and viruses from whole blood

Wang SQ, Sarenac D, Chen MH, Huang SH, Giguel FF, Kuritzkes DR, Demirci U

International Journal of Nanomedicine 2012, 7:5019-5028

Published Date: 17 September 2012

Facet-sparing lumbar decompression with a minimally invasive flexible MicroBlade Shaver® versus traditional decompression: quantitative radiographic assessment

Lauryssen C, Berven S, Mimran R, Summa C, Sheinberg M, Miller LE, Block JE

Clinical Interventions in Aging 2012, 7:257-266

Published Date: 20 July 2012

Acoustic cardiac signals analysis: a Kalman filter–based approach

Salleh SH, Hussain HS, Swee TT, Ting CM, Noor AM, Pipatsart S, Ali J, Yupapin PP

International Journal of Nanomedicine 2012, 7:2873-2881

Published Date: 11 June 2012

Anodized 20 nm diameter nanotubular titanium for improved bladder stent applications

Ece Alpaslan, Batur Ercan, Thomas J Webster

International Journal of Nanomedicine 2011, 6:219-225

Published Date: 25 January 2011

Diagnostic strategies in nasal congestion

John Krouse, Valerie Lund, Wytske Fokkens, et al

International Journal of General Medicine 2010, 3:59-67

Published Date: 17 February 2010