Abstract

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 selfassembled from a block copolymer, poly(ethylene oxide)-block-poly[N-isopropyl acrylamidestat-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 heterogenous 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 successful encapsulation of siRNA and plasmid DNA, efficient in vitro and in vivo gene transfection and expression of greenfluorescent 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.
Keywords: polymersomes, self-assembly, gene delivery, plasmid DNA, green fluorescent protein

文章链接：Nano Letters 2018, 18(9), 5562-5568.