Deprotection-Induced Morphology Transition and Immunoactivation of Glycovesicles: A Strategy of Smart Delivery Polymersomes
Deprotection-Induced Morphology Transition and Immunoactivation of Glycovesicles: A Strategy of Smart Delivery Polymersomes
复制标题
去保护诱导的糖囊泡形态转变和免疫激活：智能递送聚合物体的策略。
DOI：
10.1021/jacs.8b04731
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发表时间：
2018-07-18
影响因子：
15
通讯作者：
Jiang, Ming
中科院分区：
文献类型：
--
作者：
Qi, Wenjing;Zhang, Yufei;Jiang, Ming
我们提出了脱保护诱导嵌段共聚物自组装（DISA）；也就是说，羟基的脱保护导致了糖共聚物的原位自组装。在以往的研究中，嵌段共聚物均可溶于常见的有机溶剂。本文以水中含有预组装糖囊的保护糖块为起始材料，向前推进，取得了两项突破性成果。首先，我们观察到水中碱引发的脱保护诱导的形态转变。在去保护过程中，碳水化合物-碳水化合物的相互作用被认为有助于这种形态转变。其次，脂肪酶被发现是糖脱保护过程中有效的酶促因子，它激发了这种形态转变过程的免疫应用。当脂肪酶和模型抗原卵清蛋白（OVA）被包裹在糖囊泡内时，脂肪酶对糖的脱保护作用诱导糖囊向胶束转变，脂肪酶和卵清蛋白随之释放。当糖囊被树突状细胞（DCs）内化时，溶酶体的脂肪酶有效地诱导OVA的释放和抗原向T细胞的呈递。在此过程中，溶酶体脂肪酶在没有任何其他试剂的情况下触发糖的脱保护和蛋白质的释放。该设计的意义在于，作为递送载体，受保护的糖囊泡不仅避免了不必要的免疫激活，而且与释放的OVA一起工作；即糖载体成功激活了dc，显著提高了T细胞的提呈效率。
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.