Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle

Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the pr...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2013-04, Vol.110 (17), p.6700-6705
Main Authors: Arvizo, Rochelle R., Saha, Sounik, Wang, Enfeng, Robertson, J. David, Bhattacharya, Resham, Mukherjee, Priyabrata
Format: Article
Language:English
Subjects:
Biological Sciences
Blotting, Western
Cadherins - metabolism
Cancer
Cell growth
Cell lines
Cell membranes
Cell Proliferation - drug effects
Cells
Drug Delivery Systems
Epithelial cells
Epithelial-Mesenchymal Transition - drug effects
Epithelial-Mesenchymal Transition - physiology
Female
Gold - chemistry
Gold - pharmacology
Gold - therapeutic use
Hepatocytes
Humans
Immunohistochemistry
MAP Kinase Signaling System - drug effects
MAP Kinase Signaling System - physiology
Metastasis
Microscopy, Confocal
Microscopy, Electron, Transmission
Nanoparticles
Nanoparticles - chemistry
Nanoparticles - therapeutic use
Nanotechnology
Nanotechnology - methods
Neoplasm Metastasis - prevention & control
Ovarian cancer
Ovarian Neoplasms - drug therapy
Physical Sciences
Proteins
Real-Time Polymerase Chain Reaction
Snail Family Transcription Factors
Transcription Factors - metabolism
Tumors
Vimentin - metabolism
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Summary:Although biomedical applications of nanotechnology, which typically involve functionalized nanoparticles, have taken significant strides, biological characterization of unmodified nanoparticles remains underinvestigated. Herein we demonstrate that unmodified gold nanoparticles (AuNPs) inhibit the proliferation of cancer cells in a size- and concentration-dependent manner by abrogating MAPK-signaling. In addition, these AuNPs reverse epithelial-mesenchymal transition (EMT) in cancer cells by reducing secretion of a number of proteins involved in EMT, up-regulating E-Cadherin, and down-regulating Snail, N-Cadherin, and Vimentin. Inhibition of MAPK signaling and reversal of EMT upon AuNP treatment inhibits tumor growth and metastasis in two separate orthotopic models of ovarian cancer. Western blot analyses of tumor tissues reveal up-regulation of E-Cadherin and down-regulation of Snail and phospho-MAPK, confirming the reversal of EMT and inhibition of MAPK signaling upon AuNP treatment. The ability of a single self-therapeutic nanoparticle to abrogate signaling cascades of multiple growth factors is distinctive and purports possible medical applications as potential antitumor and antimetastatic agent.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.1214547110