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Dispersing Zwitterions into Comb Polymers for Nonviral Transfection: Experiments and Molecular Simulation
https://repo.qst.go.jp/records/47865
https://repo.qst.go.jp/records/47865d2f04b97-561a-409a-831d-0faaa59101b7
| Item type | 学術雑誌論文 / Journal Article(1) | |||||
|---|---|---|---|---|---|---|
| 公開日 | 2017-04-27 | |||||
| タイトル | ||||||
| タイトル | Dispersing Zwitterions into Comb Polymers for Nonviral Transfection: Experiments and Molecular Simulation | |||||
| 言語 | ||||||
| 言語 | eng | |||||
| 資源タイプ | ||||||
| 資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||
| 資源タイプ | journal article | |||||
| アクセス権 | ||||||
| アクセス権 | metadata only access | |||||
| アクセス権URI | http://purl.org/coar/access_right/c_14cb | |||||
| 著者 |
F., Ghobadi Ahmadreza
× F., Ghobadi Ahmadreza× Letteri, Rachel× S., Parelkar Sangram× ザオ, ユエ× Chan-Seng, Delphine× Emrick, Todd× Jayaraman, Arthi× ザオ ユエ |
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| 抄録 | ||||||
| 内容記述タイプ | Abstract | |||||
| 内容記述 | Polymer-based gene delivery vehicles benefit from the presence of hydrophilic groups that mitigate the inherent toxicity of polycations and that provide tunable polymer-DNA binding strength and stable complexes (polyplexes). However, hydrophilic groups screen charge, and as such can reduce cell uptake and transfection efficiency. We report the effect of embedding zwitterionic sulfobetaine (SB) groups in cationic comb polymers, using a combination of experiments and molecular simulations. Ring-opening metathesis polymerization (ROMP) produced comb polymers with tetralysine (K4) and SB pendent groups. Dynamic light scattering, zeta potential measurements, and fluorescence-based experiments, together with coarse-grained molecular dynamics simulations, described the effect of SB groups on the size, shape, surface charge, composition, and DNA binding strength of polyplexes formed using these comb polymers. Experiments and simulations showed that increasing SB composition in the comb polymers decreased polymer-DNA binding strength, while simulations indicated that the SB groups distributed throughout the polyplex. This allows polyplexes to maintain a positive surface charge and provide high levels of gene expression in live cells. Notably, comb polymers with nearly 50 mol % SB form polyplexes that exhibit positive surface charge similarly as polyplexes formed from purely cationic comb polymers, indicating the ability to introduce an appreciable amount of SB functionality without screening surface charge. This integrated simulation-experimental study demonstrates the effectiveness of incorporating zwitterions in polyplexes, while guiding the design of new and effective gene delivery vectors. | |||||
| 書誌情報 |
biomacromnolecules 巻 17, 号 2, p. 546-557, 発行日 2017-02 |
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| 出版者 | ||||||
| 出版者 | American Chemical Society | |||||
| ISSN | ||||||
| 収録物識別子タイプ | ISSN | |||||
| 収録物識別子 | 1525-7797 | |||||
| DOI | ||||||
| 識別子タイプ | DOI | |||||
| 関連識別子 | 10.1021/acs.biomac.5b01462 | |||||
