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

EpCAM-Antibody-Labeled Noncytotoxic Polymer Vesicles for Cancer Stem Cells-Targeted Delivery of Anticancer Drug and siRNA

Cancer stem cells (CSCs) have the capability to initiate tumor, to sustain tumor growth, to maintain the heterogeneity of tumor, and are closely linked to the failure of chemotherapy due to their self-renewal and multilineage differentiation capability with an innate resistance to cytotoxic agents. Herein, we designed and synthesized a novel anti-EpCAM (epithelial cell adhesion molecule)-monoclonal-antibody-labeled CSCs-targeting, noncytotoxic and pH-sensitive block copolymer vesicle as a nanocarrier of anticancer drug and siRNA (to overcome CSCs drug resistance by silencing the expression of oncogenes). This vesicle shows high delivery efficacy of both anticancer drug doxorubicin hydrochloride (DOX·HCl) and siRNA to the CSCs because it is labeled by the monoclonal antibodies to the CSCs-surface-specific marker. Compared to non-CSCs-targeting vesicles, the DOX·HCl or siRNA loaded CSCs-targeting vesicles exhibited much better CSCs killing and tumor growth inhibition capabilities with lower toxicity to normal cells (IC_50,DOX decreased by 80%), demonstrating promising potential applications in nanomedicine