- The rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M (n) similar to 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer toThe rational design of a polyplex gene carrier aims to balance maximal effectiveness of nucleic acid transfection into cells with minimal adverse effects. Depsipeptide blocks with an M (n) similar to 5 kDa exhibiting strong physical interactions were conjugated with PEI moieties (2.5 or 10 kDa) to di- and triblock copolymers. Upon nanoparticle formation and complexation with DNA, the resulting polyplexes (sizes typically 60-150 nm) showed remarkable stability compared to PEI-only or lipoplex and facilitated efficient gene delivery. Intracellular trafficking was visualized by observing fluorescence-labeled pDNA and highlighted the effective cytoplasmic uptake of polyplexes and release of DNA to the perinuclear space. Specifically, a triblock copolymer with a middle depsipeptide block and two 10 kDa PEI swallowtail structures mediated the highest levels of transgenic VEGF secretion in mesenchymal stem cells with low cytotoxicity. These nanocarriers form the basis for a delivery platform technology, especially for gene transfer to primary human cells.…
MetadatenAuthor details: | Weiwei WangGND, Toufik NaolouORCiD, Nan Ma, Zijun DengGND, Xun Xu, Ulrich MansfeldGND, Christian WischkeORCiDGND, Manfred GossenORCiDGND, Axel T. NeffeORCiDGND, Andreas LendleinORCiDGND |
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DOI: | https://doi.org/10.1021/acs.biomac.7b01034 |
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ISSN: | 1525-7797 |
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ISSN: | 1526-4602 |
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Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/28954190 |
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Title of parent work (English): | Biomacromolecules : an interdisciplinary journal focused at the interface of polymer science and the biological sciences |
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Publisher: | American Chemical Society |
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Place of publishing: | Washington |
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Publication type: | Article |
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Language: | English |
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Year of first publication: | 2017 |
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Publication year: | 2017 |
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Release date: | 2020/04/20 |
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Volume: | 18 |
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Number of pages: | 15 |
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First page: | 3819 |
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Last Page: | 3833 |
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Funding institution: | Deutsche Forschungsgemeinschaft (DFG) via Collaborative Research Centre [1112]; Helmholtz Association; Federal Ministry of Education and Research, Germany in the program Health Research [13GW0098] |
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Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Chemie |
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Peer review: | Referiert |
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