Center for Biomedical Materials and Interfaces, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P. R. China.
Molecular Medicine, National Heart and Lung Institute, Imperial College London, London, SW7 2AZ, UK.
Angew Chem Int Ed Engl. 2018 Aug 6;57(32):10268-10272. doi: 10.1002/anie.201806941. Epub 2018 Jul 13.
A biodegradable two-dimensional (2D) delivery platform based on loading black phosphorus nanosheets (BPs) with Cas9 ribonucleoprotein engineered with three nuclear localization signals (NLSs) at C terminus (Cas9N3) is successfully established. The Cas9N3-BPs enter cells effectively via membrane penetration and endocytosis pathways, followed by a BPs biodegradation-associated endosomal escape and cytosolic releases of the loaded Cas9N3 complexes. The Cas9N3-BPs thus provide efficient genome editing and gene silencing in vitro and in vivo at a relatively low dose as compared with other nanoparticle-based delivery platforms. This biodegradable 2D delivery platform offers a versatile cytosolic delivery approach for CRISPR/Cas9 ribonucleoprotein and other bioactive macromolecules for biomedical applications.
一种基于负载黑磷纳米片（BPs）的可生物降解二维（2D）递药平台被成功建立，该平台所负载的黑磷纳米片上整合了带有三个核定位信号（NLSs）的 C 端工程化 Cas9 核糖核蛋白（Cas9N3）。Cas9N3-BPs 通过细胞膜渗透和内吞作用途径有效地进入细胞，随后 BPs 相关的溶酶体逃逸和负载的 Cas9N3 复合物在细胞质中的释放。与其他基于纳米颗粒的递药平台相比，Cas9N3-BPs 以相对较低的剂量在体外和体内实现了高效的基因组编辑和基因沉默。这种可生物降解的 2D 递药平台为 CRISPR/Cas9 核糖核蛋白和其他生物活性大分子提供了一种多功能的胞质递药方法，可用于生物医学应用。
