Gao Lei, Wang Tingting, Jia Keke, Wu Xuan, Yao Chenhao, Shao Wei, Zhang Dongmei, Hu Xiao-Yu, Wang Leyong
Key Laboratory of Mesoscopic Chemistry of MOE, Collaborative Innovation Center of Chemistry for Life Sciences, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, 210023, P. R. China.
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing, 210023, P. R. China.
Chemistry. 2017 May 11;23(27):6605-6614. doi: 10.1002/chem.201700345. Epub 2017 Apr 20.
The stimuli-responsive behavior of supramolecular nanocarriers is crucial for their potential applications as smart drug delivery systems. We hereby constructed a glucose-responsive supramolecular drug delivery system based on the host-guest interaction between a water-soluble pillar[5]arene (WP5) and a pyridylboronic acid derivative (G) for insulin delivery and controlled release under physiological conditions. The approach represents the ideal treatment of diabetes mellitus. The drug loading and in vitro drug release experiments demonstrated that large molecular weight insulin could be encapsulated into the vesicles with high loading efficiency, which, to our knowledge, is the first example of small-size supramolecular vesicles with excellent encapsulation capacity of a large protein molecule. Moreover, FITC-labeled insulin was used to evaluate the release behavior of insulin, and it was demonstrated that high glucose concentration could facilitate the quick release of insulin, suggesting a smart drug delivery system for potential application in controlled insulin release only under hyperglycemic conditions. Finally, we demonstrated that these supramolecular nanocarriers have good cytocompatibility, which is essential for their further biomedical applications. The present study provides a novel strategy for the construction of glucose-responsive smart supramolecular drug delivery systems, which has potential applications for the treatment of diabetes mellitus.
超分子纳米载体的刺激响应行为对于其作为智能药物递送系统的潜在应用至关重要。我们在此基于水溶性柱[5]芳烃（WP5）与吡啶硼酸衍生物（G）之间的主客体相互作用构建了一种葡萄糖响应性超分子药物递送系统，用于在生理条件下递送和控释胰岛素。该方法代表了糖尿病的理想治疗方法。药物负载和体外药物释放实验表明，大分子量胰岛素能够以高负载效率包封于囊泡中，据我们所知，这是具有优异大蛋白分子包封能力的小尺寸超分子囊泡的首个实例。此外，用异硫氰酸荧光素标记的胰岛素来评估胰岛素的释放行为，结果表明高葡萄糖浓度可促进胰岛素的快速释放，这表明该智能药物递送系统仅在高血糖条件下在胰岛素控释方面具有潜在应用价值。最后，我们证明这些超分子纳米载体具有良好的细胞相容性，这对于它们进一步的生物医学应用至关重要。本研究为构建葡萄糖响应性智能超分子药物递送系统提供了一种新策略，该系统在糖尿病治疗方面具有潜在应用价值。
