TY - JOUR
T1 - Inhibition of tumor growth and metastasis by a self-therapeutic nanoparticle
AU - Arvizo, Rochelle R.
AU - Saha, Sounik
AU - Wang, Enfeng
AU - Robertson, J. David
AU - Bhattacharya, Resham
AU - Mukherjee, Priyabrata
PY - 2013/4/23
Y1 - 2013/4/23
N2 - 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-mes- enchymal 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.
AB - 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-mes- enchymal 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.
KW - Drug delivery
KW - Heparin-binding growth factors
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U2 - 10.1073/pnas.1214547110
DO - 10.1073/pnas.1214547110
M3 - Article
C2 - 23569259
AN - SCOPUS:84876871170
SN - 0027-8424
VL - 110
SP - 6700
EP - 6705
JO - Proceedings of the National Academy of Sciences of the United States of America
JF - Proceedings of the National Academy of Sciences of the United States of America
IS - 17
ER -