Liang Ping, Liu Chuan-Jun, Zhuo Ren-Xi, Cheng Si-Xue
Key Laboratory of Biomedical Polymers of Ministry of Education, Department of Chemistry, Wuhan University, Wuhan 430072, People's Republic of China.
J Mater Chem B. 2013 Sep 14;1(34):4243-4250. doi: 10.1039/c3tb20455c. Epub 2013 Jul 8.
With the aim to develop a facile strategy to prepare multi-functional drug carriers and construct a new smart drug delivery platform, we prepared KALA/heparin-biotin/heparin/chitosan/CaCO (KALA/HPB/HP/CTS/CaCO) hybrid nanoparticles with pH sensitivity, active targeting properties and cell penetrating abilities. All the functional components were introduced to the nanoparticles by self-assembly. The usage of the hybrid nanoparticles as an anti-cancer drug delivery platform was investigated. For comparison, HP/CTS, HP/CTS/CaCO and HPB/HP/CTS/CaCO hybrid nanoparticles were also prepared. The sizes and size distributions of the nanoparticles were determined by dynamic light scattering (DLS). The structure and morphology of the nanoparticles were characterized by X-ray photoelectron spectroscopy (XPS), transmission electron microscopy (TEM), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analyzer (TGA). Doxorubicin hydrochloride (DOX) was loaded in the hybrid nanoparticles and the in vitro release study showed that the CaCO containing nanoparticles exhibited pH sensitive release behavior and could efficiently sustain the drug release. In vitro cellular cytotoxicity indicated the blank hybrid nanoparticles had good biocompatibility. DOX loaded KALA/HPB/HP/CTS/CaCO hybrid nanoparticles exhibited the strongest tumor cell inhibition effects compared with free DOX and other DOX loaded nanoparticles because of the enhanced cell uptake caused by the cell penetrating peptide and the biotin moiety in the nanoparticles. All those results indicated that the KALA/HPB/HP/CTS/CaCO hybrid nanoparticles could be promising carriers for drug delivery.
为了开发一种简便的策略来制备多功能药物载体并构建新型智能药物递送平台，我们制备了具有pH敏感性、主动靶向特性和细胞穿透能力的KALA/肝素-生物素/肝素/壳聚糖/CaCO（KALA/HPB/HP/CTS/CaCO）杂化纳米粒子。所有功能成分均通过自组装引入到纳米粒子中。研究了杂化纳米粒子作为抗癌药物递送平台的用途。作为比较，还制备了HP/CTS、HP/CTS/CaCO和HPB/HP/CTS/CaCO杂化纳米粒子。通过动态光散射（DLS）测定纳米粒子的尺寸和尺寸分布。通过X射线光电子能谱（XPS）、透射电子显微镜（TEM）、傅里叶变换红外光谱（FTIR）和热重分析仪（TGA）对纳米粒子的结构和形态进行了表征。将盐酸多柔比星（DOX）负载到杂化纳米粒子中，体外释放研究表明含CaCO的纳米粒子表现出pH敏感的释放行为，并且能够有效地维持药物释放。体外细胞毒性表明空白杂化纳米粒子具有良好的生物相容性。与游离DOX和其他负载DOX的纳米粒子相比，负载DOX的KALA/HPB/HP/CTS/CaCO杂化纳米粒子表现出最强的肿瘤细胞抑制作用，这是由于纳米粒子中的细胞穿透肽和生物素部分导致细胞摄取增强。所有这些结果表明，KALA/HPB/HP/CTS/CaCO杂化纳米粒子有望成为药物递送载体。
