Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins.
Polymeric Nanoparticles Amenable to Simultaneous Installation of Exterior Targeting and Interior Therapeutic Proteins.
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DOI：
10.1002/anie.201509183
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发表时间：
2016-03-01
期刊：
影响因子：
--
通讯作者：
Farokhzad OC
中科院分区：
文献类型：
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作者：
Zhu X;Wu J;Shan W;Tao W;Zhao L;Lim JM;D'Ortenzio M;Karnik R;Huang Y;Shi J;Farokhzad OC
有效递送治疗性蛋白质是一项艰巨的挑战。在此，我们使用具有广泛的阳离子和疏水特征的独特聚合物家族，开发了一种新型纳米颗粒（NP）平台，能够在颗粒表面安装蛋白质配体，并同时通过自组装程序在内部携带治疗性蛋白质。纳米粒子内加载的治疗性蛋白质（例如胰岛素）表现出持续且可调节的释放，而表面包被的蛋白质配体（例如转铁蛋白）被证明可以改变纳米粒子的细胞行为。体内结果表明，转铁蛋白包被的纳米粒子可以有效地穿过肠上皮进行口服胰岛素输送，从而产生显着的降血糖反应。通过单一自组装步骤开发了一种新型聚合物纳米颗粒平台，该平台能够在颗粒表面安装蛋白质配体，同时在内部携带治疗性蛋白质。转铁蛋白的表面涂层极大地改变了纳米颗粒的细胞行为，并通过胞吞作用增强了它们的跨上皮转运。通过将胰岛素装载在转铁蛋白包被的纳米颗粒内，口服给药后会引起显着的低血糖反应。
Effective delivery of therapeutic proteins 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. A novel polymeric nanoparticle platform that is capable of installing protein ligands on the particle surface and simultaneously carrying therapeutic proteins inside was developed in a single self-assembly step. The surface coating with transferrin drastically changes the cellular behavior of the nanoparticles and enhances their transepithelial transport via transcytosis. By loading insulin within the transferrin-coated nanoparticles, a notable hypoglycemic response is elicited following oral administration.