The State Key Laboratory of Molecular Engineering of Polymers and Department of Macromolecular Science , Fudan University , Shanghai , 200433 China.
Soft Matter and Functional Materials , Helmholtz-Zentrum Berlin für Materialien und Energie , 14109 Berlin , Germany.
J Am Chem Soc. 2018 Jul 18;140(28):8851-8857. doi: 10.1021/jacs.8b04731. Epub 2018 Jul 2.
We proposed the deprotection-induced block copolymer self-assembly (DISA); that is, the deprotection of hydroxyl groups resulted in in situ self-assembly of glycopolymers. In the previous studies, block copolymers soluble in common organic solvents were employed as the starting material. In this paper, by using the protected glyco-block containing preassembled glycovesicles in water as the starting material, we moved forward and made two exceeding achievements. First, we have observed a deprotection-induced morphology transition triggered by alkali in water. The carbohydrate-carbohydrate interactions were considered to contribute to such a morphology transition during deprotection. Second, lipase was found to be an efficient enzymatic trigger in the sugar deprotection, which motivates the immune-application of this morphology transition process. When lipase and a model antigen, ovalbumin (OVA), were encapsulated inside the glycovesicles, the deprotection of sugars by lipase induced the transition of vesicles to micelles and the lipase and OVA were released accordingly. When glycovesicles were internalized by dentritic cells (DCs), the lipase from lysosomes efficiently induced the release of OVA and presentation of antigen to T cells. During the process, lysosomal lipase performed as a trigger on the deprotection of sugars and the release of protein without any other reagents. The significance of this design is that as a delivery vehicle, the protected glycovesicles not only avoided unnecessary immune activation but also worked with the released OVA together; that is, the glycovehicle successfully activated DCs and improved the presentation efficiency of T cells remarkably.
我们提出了去保护诱导嵌段共聚物自组装（DISA）；也就是说，羟基的去保护导致糖聚物的原位自组装。在以前的研究中，使用了可溶于常见有机溶剂的嵌段共聚物作为起始材料。在本文中，我们通过使用预先在水中组装的含保护基的糖基嵌段共聚物作为起始材料，向前迈进了两步，并取得了两个卓越的成就。首先，我们观察到了在水中由碱触发的去保护诱导的形态转变。在去保护过程中，糖基-糖基相互作用被认为有助于这种形态转变。其次，发现脂肪酶是糖基去保护的一种有效酶触发剂，这激发了该形态转变过程在免疫方面的应用。当脂肪酶和模型抗原卵清蛋白（OVA）被包裹在糖泡囊中时，脂肪酶对糖的去保护诱导了泡囊向胶束的转变，同时脂肪酶和 OVA 也随之释放。当糖泡囊被树突状细胞（DC）内化时，溶酶体中的脂肪酶有效地诱导了 OVA 的释放和抗原向 T 细胞的呈递。在这个过程中，溶酶体中的脂肪酶作为糖去保护和蛋白质释放的触发剂，而无需使用任何其他试剂。这种设计的意义在于，作为一种递送载体，保护的糖泡囊不仅避免了不必要的免疫激活，而且与释放的 OVA 一起发挥作用；也就是说，糖载体成功地激活了 DC，并显著提高了 T 细胞的呈递效率。
