Dually Gated Polymersomes for Gene Delivery

An ideal gene carrier requires an excellent gating system to efficiently load, protect, deliver, and release environmentally sensitive nucleic acids on demand. Presented in this communication is a polymersome with a “boarding gate” and a “debarkation gate” in the membrane to complete the above impor...

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Bibliographic Details
Published in:Nano letters 2018-09, Vol.18 (9), p.5562-5568
Main Authors: Wang, Fangyingkai, Gao, Jingyi, Xiao, Jiangang, Du, Jianzhong
Format: Article
Language:English
Subjects:
Acrylamides - chemistry
Animals
Cell Line
Coumarins - chemistry
DNA - administration & dosage
DNA - genetics
Gene Transfer Techniques
Green Fluorescent Proteins - genetics
Humans
Hydrogen-Ion Concentration
Hydrophobic and Hydrophilic Interactions
Methacrylates - chemistry
Mice, Nude
Plasmids - administration & dosage
Plasmids - genetics
Polyethylene Glycols - chemistry
RNA, Small Interfering - administration & dosage
RNA, Small Interfering - genetics
Temperature
Transfection - methods
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Summary:An ideal gene carrier requires an excellent gating system to efficiently load, protect, deliver, and release environmentally sensitive nucleic acids on demand. Presented in this communication is a polymersome with a “boarding gate” and a “debarkation gate” in the membrane to complete the above important missions. This dually gated polymersome is self-assembled from a block copolymer, poly­(ethylene oxide)-block-poly­[N-isopropylacrylamide-stat-7-(2-methacryloyloxyethoxy)-4-methylcoumarin-stat-2-(diethylamino)­ethyl methacrylate] [PEO-b-P­(NIPAM-stat-CMA-stat-DEA)]. The hydrophilic PEO chains form the coronas of the polymersome, whereas the temperature and pH-sensitive P­(NIPAM-stat-CMA-stat-DEA) block forms the dually gated heterogeneous membrane. The temperature-controlled “boarding gate” can be opened at room temperature for facile encapsulation of siRNA and plasmid DNA into polymersomes directly in aqueous solution. The “debarkation gate” can be triggered by proton sponge effect for intracellular release. Biological studies confirmed the successful encapsulation of siRNA and plasmid DNA, efficient in vitro and in vivo gene transfection, and the expression of green fluorescent protein (GFP) from GFP-encoding plasmid, suggesting that this kind of polymersome with a dual gating system can serve as an excellent biomacromolecular shuttle for gene delivery and other biological applications.
ISSN:1530-6984
1530-6992
DOI:10.1021/acs.nanolett.8b01985