Transfection mechanisms of polyplexes, lipoplexes, and stealth liposomes in α₅β₁ integrin bearing DLD-1 colorectal cancer cells

Receptor targeted, PEGylated transfection agents can improve stability and delivery specificity of current cationic lipid and polymer based nonviral gene delivery vehicles, but their mode of transfection is poorly understood. We therefore investigated the transfection mechanisms of 1,2-dioleoyl-3-tr...

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Veröffentlicht in:Langmuir : the ACS journal of surfaces and colloids. - 1992. - 30(2014), 13 vom: 08. Apr., Seite 3802-10
1. Verfasser: Adil, Maroof M (VerfasserIn)
Weitere Verfasser: Erdman, Zachary S, Kokkoli, Efrosini
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2014
Zugriff auf das übergeordnete Werk:Langmuir : the ACS journal of surfaces and colloids
Schlagworte:Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S. Fatty Acids, Monounsaturated Integrin alpha5beta1 Liposomes Phosphatidylethanolamines Quaternary Ammonium Compounds 1,2-dielaidoylphosphatidylethanolamine 76391-83-8 mehr... Polyethyleneimine 9002-98-6 Luciferases EC 1.13.12.- 1,2-dioleoyloxy-3-(trimethylammonium)propane MR86K0XRQP
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245 1 0 |a Transfection mechanisms of polyplexes, lipoplexes, and stealth liposomes in α₅β₁ integrin bearing DLD-1 colorectal cancer cells 
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520 |a Receptor targeted, PEGylated transfection agents can improve stability and delivery specificity of current cationic lipid and polymer based nonviral gene delivery vehicles, but their mode of transfection is poorly understood. We therefore investigated the transfection mechanisms of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP)/1,2-dioleoyl-sn-glycero-3-phosphoethanolamine (DOPE) lipoplexes, branched polyethylenimine (bPEI) polyplexes, and bPEI encapsulated in either PEGylated (stealth) nontargeted liposomes or PR_b peptide (targeted to α5β1 integrin) functionalized stealth liposomes in DLD-1 colorectal cancer cells in vitro with gene expression assays, flow cytometry and confocal microscopy. DOTAP/DOPE and PR_b functionalized stealth liposomes mediated higher gene expression compared to nontargeted stealth liposomes and bPEI. However DOTAP/DOPE was internalized slowly leading to lower levels of DNA uptake. In contrast, despite high internalization of bPEI polyplexes, gene expression levels were low as DNA was unable to escape from the endosomes. Nontargeted stealth liposomes also mediated low gene expression due to low amounts of DNA internalized and slow internalization kinetics. PR_b functionalized stealth liposomes struck an optimal balance among these transfection agents with efficient transfection arising from fast integrin mediated internalization kinetics, high amounts of DNA uptake, and endosomal escape. We found α5β1 integrin to be a valuable target for gene delivery and that the caveolar endocytic pathway may offer an advantage to receptor targeted PEGylated transfection agents in DLD-1 cells 
650 4 |a Journal Article 
650 4 |a Research Support, Non-U.S. Gov't 
650 4 |a Research Support, U.S. Gov't, Non-P.H.S. 
650 7 |a Fatty Acids, Monounsaturated  |2 NLM 
650 7 |a Integrin alpha5beta1  |2 NLM 
650 7 |a Liposomes  |2 NLM 
650 7 |a Phosphatidylethanolamines  |2 NLM 
650 7 |a Quaternary Ammonium Compounds  |2 NLM 
650 7 |a 1,2-dielaidoylphosphatidylethanolamine  |2 NLM 
650 7 |a 76391-83-8  |2 NLM 
650 7 |a Polyethyleneimine  |2 NLM 
650 7 |a 9002-98-6  |2 NLM 
650 7 |a Luciferases  |2 NLM 
650 7 |a EC 1.13.12.-  |2 NLM 
650 7 |a 1,2-dioleoyloxy-3-(trimethylammonium)propane  |2 NLM 
650 7 |a MR86K0XRQP  |2 NLM 
700 1 |a Erdman, Zachary S  |e verfasserin  |4 aut 
700 1 |a Kokkoli, Efrosini  |e verfasserin  |4 aut 
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