Document Detail


Targeted delivery of siRNA-generating DNA nanocassettes using multifunctional nanoparticles.
MedLine Citation:
PMID:  23292656     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Molecular therapy using a small interfering RNA (siRNA) has shown promise in the development of novel therapeutics. Various formulations have been used for in vivo delivery of siRNAs. However, the stability of short double-stranded RNA molecules in the blood and efficiency of siRNA delivery into target organs or tissues following systemic administration have been the major issues that limit applications of siRNA in human patients. In this study, multifunctional siRNA delivery nanoparticles are developed that combine imaging capability of nanoparticles with urokinase plasminogen activator receptor-targeted delivery of siRNA expressing DNA nanocassettes. This theranostic nanoparticle platform consists of a nanoparticle conjugated with targeting ligands and double-stranded DNA nanocassettes containing a U6 promoter and a shRNA gene for in vivo siRNA expression. Targeted delivery and gene silencing efficiency of firefly luciferase siRNA nanogenerators are demonstrated in tumor cells and in animal tumor models. Delivery of survivin siRNA expressing nanocassettes into tumor cells induces apoptotic cell death and sensitizes cells to chemotherapy drugs. The ability of expression of siRNAs from multiple nanocassettes conjugated to a single nanoparticle following receptor-mediated internalization should enhance the therapeutic effect of the siRNA-mediated cancer therapy.
Authors:
Young-Seok Cho; Gee Young Lee; Hari Krishna Sajja; Weiping Qian; Zehong Cao; Weiling He; Prasanthi Karna; Xiaoyuan Chen; Hui Mao; Y Andrew Wang; Lily Yang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2013-01-06
Journal Detail:
Title:  Small (Weinheim an der Bergstrasse, Germany)     Volume:  9     ISSN:  1613-6829     ISO Abbreviation:  Small     Publication Date:  2013 Jun 
Date Detail:
Created Date:  2013-06-04     Completed Date:  2014-01-06     Revised Date:  2014-04-14    
Medline Journal Info:
Nlm Unique ID:  101235338     Medline TA:  Small     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  1964-73     Citation Subset:  IM    
Copyright Information:
Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
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MeSH Terms
Descriptor/Qualifier:
Cell Line, Tumor
Gene Silencing
Humans
Inhibitor of Apoptosis Proteins / genetics
Nanoparticles / chemistry*
RNA, Small Interfering / genetics*
Grant Support
ID/Acronym/Agency:
P50 CA128613/CA/NCI NIH HHS; P50CA128613/CA/NCI NIH HHS; R01 CA154129/CA/NCI NIH HHS; R01 CA154846/CA/NCI NIH HHS; R01 CA163256/CA/NCI NIH HHS; R01CA154129A01/CA/NCI NIH HHS; RC2 CA148265/CA/NCI NIH HHS; U01 CA151810/CA/NCI NIH HHS; U01CA151810/CA/NCI NIH HHS; U54 CA119338/CA/NCI NIH HHS; U54 CA119338/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/BIRC5 protein, human; 0/Inhibitor of Apoptosis Proteins; 0/RNA, Small Interfering

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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