State Key Laboratory of Organic-Inorganic Composites, Beijing University of Chemical Technology, Beijing 100029, China.
Research Center of the Ministry of Education for High Gravity Engineering and Technology, Beijing University of Chemical Technology, Beijing 100029, China.
Nanoscale. 2022 Feb 17;14(7):2793-2801. doi: 10.1039/d2nr00040g.
The intrinsic properties and structure of carrier materials, as well as the drug-loading method, are crucial to the fabrication of high-performance controlled drug release systems. Metal-organic frameworks (MOFs) have attracted great attention in drug delivery due to their rich variety and very precisely designable structures, but their inherent small pores limit their application towards large-size drug molecules. Herein, we report a facile and efficient approach for the construction of hierarchically porous ZIF-8 (HP-ZIF-8) by spray drying. The homogeneously distributed mesopores, which result from the interspaces in the closely arranged nanosized ZIF-8 (N-ZIF-8), can be tuned by adjusting the primary particle size. More importantly, a drug (doxorubicin (DOX), for example) can be simultaneously encapsulated during the fabrication process of HP-ZIF-8, achieving a high loading rate of 79% and an encapsulation efficiency of 79%. Furthermore, we demonstrate that the obtained DOX@HP-ZIF-8 is a pH-responsive system and the release can also be controlled by the mesopore size. Although HP-ZIF-8 shows obvious advantages in drug loading and release performance compared with N-ZIF-8 loaded with DOX by the same solvent adsorption approach, DOX@HP-ZIF-8 displays significantly increased loading capacity (more than 3 times) and the slowest release rate due to its drug-loading method. Their therapeutic efficacy on HeLa cells has also been proved. These findings have important implications for the construction of HP-MOFs as drug carriers and will also present a new platform for controlled drug release and biomedical applications.
载体材料的固有性质和结构以及药物加载方法对于制备高性能控释药物释放系统至关重要。金属-有机骨架（MOFs）由于其丰富的种类和非常可设计的结构在药物传递中受到了极大的关注，但它们固有的小孔径限制了它们在大尺寸药物分子方面的应用。在此，我们通过喷雾干燥法报告了一种构建分级多孔 ZIF-8（HP-ZIF-8）的简便高效方法。均匀分布的中孔是由紧密排列的纳米 ZIF-8（N-ZIF-8）之间的间隔形成的，可以通过调节初级粒径来调节。更重要的是，药物（例如阿霉素（DOX））可以在 HP-ZIF-8 的制备过程中同时被包封，实现了 79%的高载药率和 79%的包封效率。此外，我们证明了所得到的 DOX@HP-ZIF-8 是一种 pH 响应体系，并且可以通过中孔尺寸来控制释放。尽管与通过相同溶剂吸附方法负载 DOX 的 N-ZIF-8 相比，DOX@HP-ZIF-8 在药物负载和释放性能方面表现出明显的优势，但由于其药物负载方法，DOX@HP-ZIF-8 显示出明显增加的载药量（超过 3 倍）和最慢的释放速率。它们对 HeLa 细胞的治疗效果也已得到证实。这些发现对于构建 HP-MOFs 作为药物载体具有重要意义，也将为控制药物释放和生物医学应用提供一个新的平台。
