College of Polymer Science and Engineering, State Key Laboratory of Polymer Materials Engineering, Sichuan University, Chengdu, 610065, China.
Angew Chem Int Ed Engl. 2021 Oct 4;60(41):22529-22536. doi: 10.1002/anie.202109637. Epub 2021 Sep 9.
In nature, the folding and conformation of proteins can control the cell or organelle membrane permeability and regulate the life activities. Here we report the first example of synthetic polypeptide vesicles that regulate their permeability via ordered transition of secondary conformations, in a manner similar to biological systems. The polymersomes undergo a β-sheet to α-helix transition in response to reactive oxygen species (ROS), leading to wall thinning without loss of vesicular integrity. The change of membrane structure increases the vesicular permeability and enables specific transport of payloads with different molecular weights. As a proof-of-concept, the polymersomes encapsulating enzymes could serve as nanoreactors and carries for glucose-stimulated insulin secretion in vivo inspired by human glucokinase, resulting in safe and effective treatment of type 1 diabetes mellitus in mouse models. This study will help understand the biology of biomembranes and facilitate the engineering of nanoplatforms for biomimicry, biosensing, and controlled delivery applications.
在自然界中，蛋白质的折叠和构象可以控制细胞膜或细胞器的通透性，调节生命活动。在这里，我们报告了第一个通过有序的二级构象转变来调节其通透性的合成多肽囊泡的例子，这种方式类似于生物系统。聚合物囊泡对活性氧（ROS）的响应发生β-折叠到α-螺旋的转变，导致壁变薄而不会破坏囊泡的完整性。膜结构的变化增加了囊泡的通透性，并能够实现不同分子量的有效载荷的特异性运输。作为概念验证，受人类葡萄糖激酶启发，包封酶的聚合物囊泡可以作为纳米反应器和载体，用于体内葡萄糖刺激的胰岛素分泌，从而在 1 型糖尿病小鼠模型中实现安全有效的治疗。这项研究将有助于理解生物膜的生物学，并促进用于仿生、生物传感和控制释放应用的纳米平台的工程设计。
