Li Chang, Wu Gang, Ma Rujiang, Liu Yong, Liu Ying, Lv Juan, An Yingli, Shi Linqi
State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Functional Polymer Materials of Ministry of Education, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), Nankai University, Tianjin 300071, China.
ACS Biomater Sci Eng. 2018 Jun 11;4(6):2007-2017. doi: 10.1021/acsbiomaterials.7b00546. Epub 2017 Nov 7.
Protein drugs play a significant role in the treatment of many diseases such as diabetes, cancers, and immune system diseases. Though polymeric nanocarriers have been designed to deliver protein drugs for prolonging circulation lifetime and providing stimuli-triggered release, problems are still often encountered including lower loading efficiency and capacity as well as poor circulation stability because of the weak interaction between protein drugs and nanocarriers. Herein, we described a new kind of bifunctional polymeric nanogels for efficient loading and glucose-triggered release of insulin. Biodegradable poly(-isopropylacrylamide) (PNIPAM)-based nanogels was synthesized with nitrilotriacetic acid (NTA) and phenylboronic acid (PBA) as functional groups and ethylene glycol dimethacrylate (EGDMA) as cross-linker. The NTA groups could specifically bind imidazole-containing protein drugs such as insulin via chelated zinc ions, leading an efficient loading of insulin. The structure, morphology, and drug-loading properties of the nanogels were well-characterized, and glucose-triggered insulin release was achieved based on the glucose-responsiveness of PBA groups. MTT assay and enzymatic degradation revealed good biocompatibility and biodegradability for the nanogels. This kind of bifunctional nanogels would be promising candidates for glucose-responsive delivery of insulin in the future.
蛋白质药物在治疗许多疾病如糖尿病、癌症和免疫系统疾病中发挥着重要作用。尽管已经设计了聚合物纳米载体来递送蛋白质药物以延长循环寿命并实现刺激触发释放，但由于蛋白质药物与纳米载体之间的相互作用较弱，仍然经常遇到诸如较低的负载效率和容量以及较差的循环稳定性等问题。在此，我们描述了一种新型的双功能聚合物纳米凝胶，用于高效负载胰岛素并实现葡萄糖触发释放。以可生物降解的聚（N-异丙基丙烯酰胺）（PNIPAM）为基础，以次氮基三乙酸（NTA）和苯硼酸（PBA）为功能基团，乙二醇二甲基丙烯酸酯（EGDMA）为交联剂合成了纳米凝胶。NTA基团可以通过螯合锌离子特异性结合含咪唑的蛋白质药物如胰岛素，从而实现胰岛素的高效负载。对纳米凝胶的结构、形态和载药性能进行了充分表征，并基于PBA基团的葡萄糖响应性实现了葡萄糖触发的胰岛素释放。MTT法和酶降解实验表明纳米凝胶具有良好的生物相容性和生物降解性。这种双功能纳米凝胶有望在未来成为葡萄糖响应性递送胰岛素的候选材料。
