中国科学院上海硅酸盐研究所陈航榕团队报道了微流体辅助pH酶双激活蛋白工程ZIFPolymer蛋白质和化疗药物共输运纳米系统增强肿瘤深部渗透。该研究于2022年1月5日发表于国际一流学术期刊《德国应用化学》。

实体瘤的非渗透屏障限制了蛋白质类药物和化疗药物在癌症治疗中的联合应用。

该文中，研究人员开发了ZIF-DOX/RA@DG将核糖核酸酶A（RA）和阿霉素（DOX）封装在具有葡聚糖基涂层（DG）的沸石咪唑盐骨架-8（ZIF-8）核心中的纳米系统。由于γ-谷氨酰转肽酶可激活的阳离子化和酸性微环境引发的降解，该纳米系统表现出双重响应性。DG涂层工艺采用微流控方法实现，该方法稳定了聚合物的响应性、ZIF-8基结构和胶囊治疗剂的生物活性。

体内实验结果证实，该纳米系统可将RA和DOX共同输送至深层不渗透性病变，具有协同抗癌治疗效果。该基于智能响应设计和微流体辅助合成策略的多药给药系统显示出巨大的临床前景。

附：英文原文

Title: Microfluidics-Assisted Engineering of pH/Enzyme Dual-Activatable ZIF@Polymer Nanosystem for Co-Delivery of Proteins and Chemotherapeutics with Enhanced Deep-Tumor Penetration

Author: Jie Shen, Ming Ma, Muhammad Shafiq, Huizhu Yu, Zhengyi Lan, Hangrong Chen

Issue&Volume: 2022-01-05

Abstract: 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-8 (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 synergistic anti-cancer therapeutic effects. Such a multi-drug delivery system based on an intelligent-responsive design and a microfluidics-assisted synthesis strategy shows great clinical prospects.

DOI: 10.1002/anie.202113703

Source: https://onlinelibrary.wiley.com/doi/10.1002/anie.202113703