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Ultrastable synergistic tetravalent RNA nanoparticles for targeting to cancers.
MedLine Citation:
PMID:  23024702     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
One of the advantages of nanotechnology is the feasibility to construct therapeutic particles carrying multiple therapeutics with defined structure and stoichiometry. The field of RNA nanotechnology is emerging. However, controlled assembly of stable RNA nanoparticles with multiple functionalities which retain their original role is challenging due to refolding after fusion. Herein, we report the construction of thermodynamically stable X-shaped RNA nanoparticles to carry four therapeutic RNA motifs by self-assembly of reengineered small RNA fragments. We proved that each arm of the four helices in the X-motif can harbor one siRNA, ribozyme, or aptamer without affecting the folding of the central pRNA-X core, and each daughter RNA molecule within the nanoparticle folds into their respective authentic structures and retains their biological and structural function independently. Gene silencing effects were progressively enhanced as the number of the siRNA in each pRNA-X nanoparticles gradually increased from one to two, three, and four. More importantly, systemic injection of ligand-containing nanoparticles into the tail-vein of mice revealed that the RNA nanoparticles remained intact and strongly bound to cancers without entering the liver, lung or any other organs or tissues, while remaining in cancer tissue for more than 8 h.
Authors:
Farzin Haque; Dan Shu; Yi Shu; Luda S Shlyakhtenko; Piotr G Rychahou; B Mark Evers; Peixuan Guo
Publication Detail:
Type:  JOURNAL ARTICLE    
Journal Detail:
Title:  Nano today     Volume:  7     ISSN:  1878-044X     ISO Abbreviation:  Nano Today     Publication Date:  2012 Aug 
Date Detail:
Created Date:  2012-10-1     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101297352     Medline TA:  Nano Today     Country:  -    
Other Details:
Languages:  ENG     Pagination:  245-257     Citation Subset:  -    
Affiliation:
Nanobiotechnology Center, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States ; Department of Pharmaceutical Sciences, College of Pharmacy, University of Kentucky, Lexington, KY 40536, United States.
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