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 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.