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)-<i>block</i>-poly­[<i>N</i>-isopropylacrylamide-<i>stat</i>-7-(2-methacryloyloxyethoxy)-4-methylcoumarin-<i>stat</i>-2-(diethylamino)­ethyl methacrylate] [PEO-<i>b</i>-P­(NIPAM-<i>stat</i>-CMA-<i>stat</i>-DEA)]. The hydrophilic PEO chains form the coronas of the polymersome, whereas the temperature and pH-sensitive P­(NIPAM-<i>stat</i>-CMA-<i>stat</i>-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

Synthesis and Mechanism Insight of a Peptide-Grafted Hyperbranched Polymer Nanosheet with Weak Positive Charges but Excellent Intrinsically Antibacterial Efficacy

Antimicrobial resistance is an increasingly problematic issue in the world and there is a present and urgent need to develop new antimicrobial therapies without drug resistance. Antibacterial polymers are less susceptible to drug resistance but they are prone to inducing serious side effects due to high positive charge. Herein we report a peptide-grafted hyperbranched polymer which can self-assemble into unusual nanosheets with highly effective intrinsically antibacterial activity but weak positive charges (+ 6.1 mV). The hyperbranched polymer was synthesized by sequential Michael addition-based thiol–ene and free radical mediated thiol–ene reactions, and followed by ring-opening polymerization of <i>N</i>-carboxyanhydrides (NCAs). The nanosheet structure was confirmed by transmission electron microscopy (TEM) and atomic force microscopy (AFM) studies. Furthermore, a novel “wrapping and penetrating” antibacterial mechanism of the nanosheets was revealed by TEM and it is the key to significantly decrease the positive charges but have a very low minimum inhibitory concentration (MIC) of 16 μg mL^–1 against typical Gram-positive and Gram-negative bacteria. Overall, our synthetic strategy demonstrates a new insight for synthesizing antibacterial nanomaterials with weak positive charges. Moreover, the unique antibacterial mechanism of our nanosheets may be extended for designing next-generation antibacterial agents without drug resistance