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Author (up) Chou, S.-T.; Leng, Q.; Scaria, P.; Kahn, J.D.; Tricoli, L.J.; Woodle, M.; Mixson, A.J.
url  doi
  Title Surface modified HK:siRNA nanoplexes with enhanced pharmacokinetics and tumor growth inhibition Type Journal Article
  Year 2013 Publication Biomacromolecules Abbreviated Journal Biomacromolecules  
  Volume Issue Pages  
  Abstract We characterized in this study the pharmacokinetics and antitumor efficacy of histidine-lysine (HK):siRNA nanoplexes modified with PEG and a cyclic RGD (cRGD) ligand targeting alphavbeta3 and alphavbeta5 integrins. With non-invasive imaging, systemically administered surface modified HK:siRNA nanoplexes showed nearly 4-fold greater blood levels, 40% higher accumulation in tumor tissue, and 60% lower luciferase activity than unmodified HK:siRNA nanoplexes. We then determined whether the surface modified HK:siRNA nanoplex carrier was more effective in reducing MDA-MB-435 tumor growth with an siRNA targeting Raf-1. Repeated systemic administration of the selected surface modified HK:siRNA nanoplexes targeting Raf-1 showed 35% greater inhibition of tumor growth than unmodified HK:siRNA nanoplexes and 60% greater inhibition of tumor growth than untreated mice. The improved blood pharmacokinetic results and tumor localization observed with the integrin-targeting surface modification of HK:siRNA nanoplexes correlated with greater tumor growth inhibition. This investigation reveals that through control of targeting ligand surface display in association with a steric PEG layer, modified HK: siRNA nanoplexes show promise to advance RNAi therapeutics in oncology and potentially other critical diseases.  
  Corporate Author Thesis  
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  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1525-7797 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23360232 Approved no  
  Call Number @ @ Serial 37525  
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