Bioresponsive hyperbranched polymers for siRNA and miRNA delivery

Autor:	Ulrik Lytt Rahbek, Anne Chauchereau, Flemming Besenbacher, Mingdong Dong, Kenneth A. Howard, Ye-Zi You, David Oupicky, Anne Færch Nielsen, Jørgen Kjems
Rok vydání:	2010
Předmět:	Lung Neoplasms Time Factors Polymers Green Fluorescent Proteins Pharmaceutical Science Microscopy Atomic Force Transfection Dithiothreitol Green fluorescent protein Electrolytes chemistry.chemical_compound RNA interference Cell Line Tumor Polyamines Humans Gene silencing Gene Silencing RNA Small Interfering Gene knockdown Chemistry Cationic polymerization Molecular biology Gene Expression Regulation Neoplastic MicroRNAs Cell culture Gene Knockdown Techniques Biophysics Oxidation-Reduction
Zdroj:	Rahbek, U L, Nielsen, A F, Dong, M, You, Y, Chauchereau, A, Oupicky, D, Besenbacher, F, Kjems, J & Howard, K A 2010, ' Bioresponsive hyperbranched polymers for siRNA and miRNA delivery ', Journal of Drug Targeting, vol. 18, no. 10, pp. 812-20 . https://doi.org/10.3109/1061186X.2010.527982
ISSN:	1029-2330 1061-186X
Popis:	This work presents the novel use of reducible hyperbranched (rHB) polymers for delivery of RNA interference (RNAi) therapeutics. Cationic poly(amido amine) hyperbranched polymers that contain different contents of reducible disulfide to nonreducible linkages (0%, 17%, 25%, and 50%) were used to form interpolyelectrolyte polyplexes with siRNA and precursor miRNA (pre-miRNA). Atomic force microscopy (AFM) revealed rHB complexes of ∼100 nm in size, which exhibited redox-activated disassembly in the presence of dithiothreitol (DTT). The complexes were avidly internalized and showed no cellular toxicity in an endogenous enhanced green fluorescence protein (EGFP) expressing H1299 human lung cancer cell line. The highest specific EGFP gene silencing (∼75%) was achieved with rHB (17%)/siRNA complexes at a weight-to-weight (w/w) ratio of 40 that correlated with the ability for this polymer to successfully transfect pre-miRNA. Evaluation of temporal silencing levels over 72 h revealed incremental knockdown that reached a maximum at 72 h for the rHB (50%) complexes, in contrast to maximum knockdown at 24 h that remained relatively consistent, thereafter, for the rHB (17%), rHB (25%), and non-rHB complexes. The role of particle disassembly for intracellular targeting and modulation of gene silencing addressed in this work are important considerations in the development of this and other next-generation delivery systems.
Databáze:	OpenAIRE
Externí odkaz:	https://explore.openaire.eu/search/publication?articleId=doi_dedup___::096ab4be6566c30cbb5455b71612e247 https://doi.org/10.3109/1061186x.2010.527982 Zobrazit plný text záznamu Plný text ve formátu PDF Plný text ve formátu HTML
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