Zhu Xi, Wu Jun, Shan Wei, Tao Wei, Zhao Lili, Lim Jong-Min, D'Ortenzio Mathew, Karnik Rohit, Huang Yuan, Shi Jinjun, Farokhzad Omid C
Key Laboratory of Drug Targeting and Drug Delivery System, Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu, 610041, China.
Laboratory of Nanomedicine and Biomaterials, Department of Anesthesiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, 02115, USA.
Angew Chem Int Ed Engl. 2016 Mar 1;55(10):3309-12. doi: 10.1002/anie.201509183. Epub 2016 Feb 5.
Effective delivery of therapeutic proteins is a formidable challenge. Herein, using a unique polymer family with a wide-ranging set of cationic and hydrophobic features, we developed a novel nanoparticle (NP) platform capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside by a self-assembly procedure. The loaded therapeutic proteins (e.g., insulin) within the NPs exhibited sustained and tunable release, while the surface-coated protein ligands (e.g., transferrin) were demonstrated to alter the NP cellular behaviors. In vivo results revealed that the transferrin-coated NPs can effectively be transported across the intestinal epithelium for oral insulin delivery, leading to a notable hypoglycemic response.
有效递送治疗性蛋白质是一项艰巨的挑战。在此，我们使用了具有一系列广泛阳离子和疏水特性的独特聚合物家族，通过自组装过程开发了一种新型纳米颗粒（NP）平台，该平台能够在颗粒表面安装蛋白质配体，并同时在内部携带治疗性蛋白质。NP 内负载的治疗性蛋白质（如胰岛素）表现出持续且可调节的释放，而表面包覆的蛋白质配体（如转铁蛋白）被证明可改变 NP 的细胞行为。体内结果表明，转铁蛋白包覆的 NPs 能够有效地穿过肠上皮用于口服胰岛素递送，从而导致显著的降血糖反应。
