Document Detail


Acid-degradable cationic poly(ketal amidoamine) for enhanced RNA interference in vitro and in vivo.
MedLine Citation:
PMID:  23240892     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Efficient delivery of small interfering RNA (siRNA) is one of major challenges in the successful applications of siRNA in clinic. In the present study, we report a new acid-degradable poly(ketal amidoamine) (PKAA) as a siRNA carrier, which has high delivery efficiency and low cytotoxicity. PKAA was designed to have acid-cleavable ketal linkages in the backbone of cationic biodegradable poly(amidoamine). PKAA efficiently self-assembled with siRNA to form nanocomplexes with a diameter of 200 nm and slightly positive charges, which are stable under physiological conditions, but rapidly release siRNA at acidic pH. PKAA exhibited sufficient buffering capability and endosomolytic activity due mainly to the presence of secondary amine groups in its backbone and rapid degradation in acidic endosomes, leading to the enhanced release of siRNA to cytoplasm. Cell culture studies demonstrated that PKAA is capable of delivering anti TNF (tumor necrosis factor)-α siRNA to lipopolysaccharide (LPS)-stimulated macrophages and significantly inhibit the expression of TNF-α. A mouse model of acetaminophen (APAP)-induced acute liver failure was used to evaluate in vivo siRNA delivery efficacy of PKAA. PKAA/anti TNF-α siRNA nanocomplexes significantly reduced the ALT (alanine transaminase) and the hepatic cellular damages in APAP-intoxicated mice. We anticipate that acid-degradable PKAA has great potential as siRNA carriers based on its excellent biocompatibility, pH sensitivity, potential endosomolytic activity and high delivery efficiency.
Authors:
Hyungsuk Lim; Joungyoun Noh; Yerang Kim; Hyungmin Kim; Jihye Kim; Gilson Khang; Dongwon Lee
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-16
Journal Detail:
Title:  Biomacromolecules     Volume:  -     ISSN:  1526-4602     ISO Abbreviation:  Biomacromolecules     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2012-12-17     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100892849     Medline TA:  Biomacromolecules     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
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