State Key Laboratory of High Performance Ceramics and Superfine Microstructures, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.
Center of Materials Science and Optoelectronics Engineering, University of Chinese Academy of Sciences, Beijing, 100049, P. R. China.
Angew Chem Int Ed Engl. 2022 Mar 28;61(14):e202113703. doi: 10.1002/anie.202113703. Epub 2022 Feb 10.
The impermeable barriers of solid tumors restrict the co-delivery of protein-based drugs and chemotherapeutics for cancer treatment. Therefore, we developed a ZIF-DOX/RA@DG nanosystem that encapsulates ribonuclease A (RA) and doxorubicin (DOX) in a zeolitic imidazolate framework (ZIF-8) core, with a dextran-based coating (DG). The nanosystem exhibits dual-responsiveness due to γ-glutamyl transpeptidase-activatable cationization and acidic microenvironment-triggered degradation. The DG-coating process was achieved using a microfluidic approach, which stabilized the polymer responsiveness, ZIF-8-based structure, and bioactivity of the encapsulated therapeutics. In vivo results confirmed that the nanosystem could co-deliver RA and DOX to deep impermeable lesions with a synergistic anticancer therapeutic effects. Such a multi-drug delivery system based on an intelligent-responsive design and a microfluidics-assisted synthesis strategy shows great clinical prospects.
实体瘤的不可渗透屏障限制了用于癌症治疗的蛋白质类药物和化疗药物的共递送。因此，我们开发了一种 ZIF-DOX/RA@DG 纳米系统，该系统将核糖核酸酶 A (RA) 和阿霉素 (DOX) 封装在沸石咪唑酯骨架 (ZIF-8) 核中，并具有基于葡聚糖的涂层 (DG)。该纳米系统由于 γ-谷氨酰转肽酶激活的阳离子化和酸性微环境触发的降解而表现出双重响应性。DG 涂层过程是使用微流控方法实现的，该方法稳定了聚合物的响应性、基于 ZIF-8 的结构和封装治疗剂的生物活性。体内结果证实，该纳米系统可以将 RA 和 DOX 共递送到深部不可渗透的病变部位，具有协同的抗癌治疗效果。这种基于智能响应设计和微流控辅助合成策略的多药物递送系统具有广阔的临床前景。
