Document Detail


Enhanced docetaxel-mediated cytotoxicity in human prostate cancer cells through knockdown of cofilin-1 by carbon nanohorn delivered siRNA.
MedLine Citation:
PMID:  22858003     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We synthesized a non-viral delivery system (f-CNH3) for small interfering RNA (siRNA) by anchoring a fourth-generation polyamidoamine dendrimer (G4-PAMAM) to carbon nanohorns (CNHs). Using this new compound, we delivered a specific siRNA designed to knockdown cofilin-1, a key protein in the regulation of cellular cytoskeleton, to human prostate cancer (PCa) cells. The carbon nanohorn (CNH) derivative was able to bind siRNA and release it in the presence of an excess of the polyanion heparin. Moreover, this hybrid nanomaterial protected the siRNA from RNAse-mediated degradation. Synthetic siRNA delivered to PCa cells by f-CNH3 decreased the cofilin-1 mRNA and protein levels to about 20% of control values. Docetaxel, the drug of choice for the treatment of PCa, produced a concentration-dependent activation of caspase-3, an increase in cell death assessed by lactate dehydrogenase release to the culture medium, cell cycle arrest and inhibition of tumor cell proliferation. All of these toxic effects were potentiated when cofilin-1 was down regulated in these cells by a siRNA delivered by the nanoparticle. This suggests that knocking down certain proteins involved in cancer cell survival and/or proliferation may potentiate the cytotoxic actions of anticancer drugs and it might be a new therapeutic approach to treat tumors.
Authors:
Francisco C Pérez-Martínez; Blanca Carrión; Maria I Lucío; Noelia Rubio; María A Herrero; Ester Vázquez; Valentín Ceña
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2012-08-02
Journal Detail:
Title:  Biomaterials     Volume:  33     ISSN:  1878-5905     ISO Abbreviation:  Biomaterials     Publication Date:  2012 Nov 
Date Detail:
Created Date:  2012-08-31     Completed Date:  2013-01-16     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  8152-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
NanoDrugs, S.L. Parque Científico y Tecnológico, 02071 Albacete, Spain.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects
Carbon / chemistry
Cell Line, Tumor
Cofilin 1 / genetics*
Dendrimers / chemistry
Genetic Therapy
Humans
Male
Nanostructures / chemistry
Nylons / chemistry
Prostatic Neoplasms / drug therapy,  genetics*,  therapy*
RNA Interference*
RNA, Small Interfering / administration & dosage*,  genetics
Taxoids / pharmacology*
Transfection
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Cofilin 1; 0/Dendrimers; 0/Nylons; 0/PAMAM-G4; 0/RNA, Small Interfering; 0/Taxoids; 15H5577CQD/docetaxel; 7440-44-0/Carbon

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