Henan and Macquarie University Joint Centre for Biomedical Innovation, School of Life Sciences, Henan University, Kaifeng, Henan, 475004, China.
Department of Biomedical Sciences, Faculty of Medicine & Health Sciences, Macquarie University, Sydney, NSW, Australia.
Angew Chem Int Ed Engl. 2019 Apr 1;58(15):4938-4942. doi: 10.1002/anie.201814289. Epub 2019 Mar 3.
Nanoparticles show great potential for drug delivery. However, suitable nanostructures capable of loading a range of drugs together with the co-delivery of siRNAs, which avoid the problem of cation-associated cytotoxicity, are lacking. Herein, we report an small interfering RNA (siRNA)-based vesicle (siRNAsome), which consists of a hydrophilic siRNA shell, a thermal- and intracellular-reduction-sensitive hydrophobic median layer, and an empty aqueous interior that meets this need. The siRNAsome can serve as a versatile nanostructure to load drug agents with divergent chemical properties, therapeutic proteins as well as co-delivering immobilized siRNAs without transfection agents. Importantly, the inherent thermal/reduction-responsiveness enables controlled drug loading and release. When siRNAsomes are loaded with the hydrophilic drug doxorubicin hydrochloride and anti-P-glycoprotein siRNA, synergistic therapeutic activity is achieved in multidrug resistant cancer cells and a tumor model.
纳米颗粒在药物输送方面显示出巨大的潜力。然而，缺乏能够同时装载多种药物并共同递送小干扰 RNA（siRNA）的合适纳米结构，从而避免阳离子相关细胞毒性的问题。在此，我们报告了一种基于小干扰 RNA（siRNA）的囊泡（siRNAsome），它由亲水性 siRNA 壳、热和细胞内还原敏感的疏水性中间层以及满足此需求的空的水相内部组成。siRNAsome 可以作为一种多功能的纳米结构，用于装载具有不同化学性质的药物制剂、治疗性蛋白质以及无需转染试剂即可共同递送固定化 siRNA。重要的是，固有的热/还原响应性能够实现药物的控制装载和释放。当 siRNAsome 负载亲水性药物盐酸多柔比星和抗 P-糖蛋白 siRNA 时，在多药耐药癌细胞和肿瘤模型中实现了协同治疗活性。
