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• W2232807008 endingPage "143" @default.
• W2232807008 startingPage "134" @default.
• W2232807008 abstract "Efficient delivery of functional nucleic acids into specific cells or tissues is still a challenge for gene therapy and largely depends on targeted delivery strategies. The folate receptor (FR) is known to be overexpressed extracellularly on a variety of human cancers and is therefore an outstanding gate for tumor-targeted Trojan horse-like delivery of therapeutics. In this study, an amphiphilic and biodegradable ternary copolymer conjugated with folate as ligand, polyethylenimine-graft-polycaprolactone-block-poly(ethylene glycol)-folate (PEI–PCL–PEG–Fol) was synthesized and evaluated for targeted siRNA delivery via folate–FR recognition. The amphiphilic character of similar polymers was shown previously to support endosomal release of endocytosed nanocarriers and to promote formation of long circulating micelles. The obtained PEI–PCL–PEG–Fol exhibited less cytotoxicity in comparison with the corresponding ternary copolymer without folate (PEI–PCL–PEG) and with unmodified PEI25kDa. Stable micelle-like polyplexes with hydrodynamic diameters about 100 nm were found to have a zeta potential of +8.6 mV, which was lower than that of micelleplexes without folate-conjugation (+13–16 mV). Nonetheless, increased cellular uptake and in vitro gene knockdown of PEI–PCL–PEG–Fol/siRNA micelleplexes were observed in SKOV-3 cells, an FR overexpressing cell line, in comparison with the nonfolate-conjugated ones. Moreover, PEI–PCL–PEG–Fol/siRNA micelleplexes exhibited excellent stability in vivo during the analysis of 120 min and a longer circulation half life than hyPEI25kDa/siRNA polyplexes. Most interestingly, the targeted delivery system yielded 17% deposition of the i.v. injected siRNA per gram in the tumor after 24 h due to the effective folate targeting and the prolonged circulation." @default.
• W2232807008 created "2016-06-24" @default.
• W2232807008 creator A5004308584 @default.
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• W2232807008 date "2015-12-16" @default.
• W2232807008 modified "2023-10-16" @default.
• W2232807008 title "Efficient and Tumor Targeted siRNA Delivery by Polyethylenimine-<i>graft</i>-polycaprolactone-<i>block</i>-poly(ethylene glycol)-folate (PEI–PCL–PEG–Fol)" @default.
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• W2232807008 doi "https://doi.org/10.1021/acs.molpharmaceut.5b00575" @default.
• W2232807008 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/26641134" @default.
• W2232807008 hasPublicationYear "2015" @default.
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