Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization

doi:10.1002/adfm.201910168

	Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization
	Wang, Aohua 1,3; Fan, Weiwei 1,3; Yang, Tiantian 1,3; He, Shufang 1,3; Yang, Yiwei 1,3; Yu, Miaorong 1; Fan, Li 2; Zhu, Quanlei 1; Guo, Shiyan 1; Zhu, Chunliu 1
刊名	ADVANCED FUNCTIONAL MATERIALS
	2020-02-14
页码	15
关键词	glucose responsive insulin secretion liver target oral drug delivery polymersomes
ISSN号	1616-301X
DOI	10.1002/adfm.201910168
通讯作者	Gan, Yong(ygan@simm.ac.cn)
英文摘要	Oral insulin therapy that targets the liver and further mimics glucose-responsive secretion holds promise for correcting defects in glucose metabolism caused by peripheral delivery. This work describes the construction of polymersomes (Pep-PMS), which are composed of glucose-responsive polymers decorated with peptides that readily bind to the ganglioside-monosialic acid (GM1) receptor in the intestinal epithelium. Pep-PMS are efficiently transported across the intestinal epithelium through GM1-mediated transcytosis, leading to their abundant accumulation in the liver. Moreover, Pep-PMS can efficiently encapsulate insulin in euglycemia and release them in hyperglycemia. Under hyperglycemic conditions, the Pep-PMS dissociate to release the encapsulated insulin in response to glucose oxidase (GOx)-induced H2O2. Surprisingly, the postprandial blood glucose levels of diabetic rats treated with Pep-PMS can be maintained even after being challenged by glucose administration. Hepatic glucose uptake and glycogen production are also elevated after treating diabetic rats with Pep-PMS, which is similar to glucose utilization in normal rats. Oral delivery systems that target the liver and serve as a reservoir for glucose-responsive insulin secretion may improve the therapeutic effect in people with diabetes.
资助项目	National Natural Science Foundation of China[81573378] ; National Natural Science Foundation of China[81703436] ; National Natural Science Foundation of China[81773651] ; Fudan-SIMM Joint Research Fund[FU-SIMM 20173006] ; NN-CAS foundation ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA12050307] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA15014200] ; Strategic Priority Research Program of Chinese Academy of Sciences[XDA12020222] ; Major International Joint Research Project of Chinese Academy of Sciences[153631KYSB20190020] ; Shanghai Sailing Program 2017[17YF1423500]
WOS关键词	ACID-N-CARBOXYANHYDRIDES ; ORAL DELIVERY ; CHOLERA-TOXIN ; FUNCTIONAL NANOPARTICLES ; SENSITIVE VESICLES ; IN-VITRO ; DRUG ; HYPOXIA ; RELEASE ; TRANSCYTOSIS
WOS研究方向	Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种	英语
出版者	WILEY-V C H VERLAG GMBH
WOS记录号	WOS:000513252200001
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/281745]
专题	中国科学院上海药物研究所
通讯作者	Gan, Yong
作者单位	1.Chinese Acad Sci, Ctr Pharmaceut Res, Shanghai Inst Mat Med, Shanghai 201203, Peoples R China 2.Novo Nordisk Res Ctr China, Bldg 2,20 Life Sci Pk Rd, Beijing 102206, Peoples R China 3.Univ Chinese Acad Sci, Sch Pharm, Beijing 10049, Peoples R China
推荐引用方式 GB/T 7714	Wang, Aohua,Fan, Weiwei,Yang, Tiantian,et al. Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization[J]. ADVANCED FUNCTIONAL MATERIALS,2020:15.
APA	Wang, Aohua.,Fan, Weiwei.,Yang, Tiantian.,He, Shufang.,Yang, Yiwei.,...&Gan, Yong.(2020).Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization.ADVANCED FUNCTIONAL MATERIALS,15.
MLA	Wang, Aohua,et al."Liver-Target and Glucose-Responsive Polymersomes toward Mimicking Endogenous Insulin Secretion with Improved Hepatic Glucose Utilization".ADVANCED FUNCTIONAL MATERIALS (2020):15.