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The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery

文献类型：期刊论文

作者Li, Jingyi3,4; Zhang, Yaqi4,5; Yu, Miaorong4; Wang, Aohua4,5; Qiu, Yu4,5; Fan, Weiwei4; Hovgaard, Lars6; Yang, Mingshi7; Li, Yiming3; Wang, Rui3
刊名ACTA PHARMACEUTICA SINICA B
出版日期2022-03-01
卷号12期号:3页码:1460-1472
关键词Ligand-modified nanoparticles Transporter Proton-coupled folate transporter Expression level Endocytosis Intracellular trafficking Diabetes Oral insulin delivery
ISSN号2211-3835
DOI10.1016/j.apsb.2021.07.024
通讯作者Wang, Rui(wr@shutcm.edu.cn) ; Li, Xiuying(Xiuying.Li@utdallas.edu) ; Gan, Yong(ygan@simm.ac.cn)
英文摘要Transporters are traditionally considered to transport small molecules rather than large-sized nanoparticles due to their small pores. In this study, we demonstrate that the upregulated intestinal transporter (PCFT), which reaches a maximum of 12.3-fold expression in the intestinal epithelial cells of diabetic rats, mediates the uptake of the folic acid-grafted nanoparticles (FNP). Specifically, the upregulated PCFT could exert its function to mediate the endocytosis of FNP and efficiently stimulate the traverse of FNP across enterocytes by the lysosome-evading pathway, Golgi-targeting pathway and basolateral exocytosis, featuring a high oral insulin bioavailability of 14.4% in the diabetic rats. Conversely, in cells with relatively low PCFT expression, the positive surface charge contributes to the cellular uptake of FNP, and FNP are mainly degraded in the lysosomes. Overall, we emphasize that the upregulated intestinal transporters could direct the uptake of ligand-modified nanoparticles by mediating the endocytosis and intracellular trafficking of ligand-modified nanoparticles via the transporter-mediated pathway. This study may also theoretically provide insightful guidelines for the rational design of transporter-targeted nanoparticles to achieve efficient drug delivery in diverse diseases. (C) 2022 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V.
WOS关键词ACID-CONJUGATED CHITOSAN ; DRUG-DELIVERY ; RECEPTOR ; ACCUMULATION ; MECHANISMS ; 5-METHYLTETRAHYDROFOLATE ; ABSORPTION ; COMPLEXES ; CARRIER
资助项目National Natural Science Foundation of China (NSFC), China[81773651] ; National Natural Science Foundation of China (NSFC), China[82025032] ; National Natural Science Foundation of China (NSFC), China[81803445] ; NN-CAS foundation ; National Key R&D Program of China, China[2020YFE0201700] ; Major International Joint Research Project of Chinese Academy of Sciences, China[153631KYSB20190020]
WOS研究方向Pharmacology & Pharmacy
语种英语
WOS记录号WOS:000782810600002
出版者INST MATERIA MEDICA, CHINESE ACAD MEDICAL SCIENCES
源URL[http://119.78.100.183/handle/2S10ELR8/299797]  
专题新药研究国家重点实验室
通讯作者Wang, Rui; Li, Xiuying; Gan, Yong
作者单位1.Univ Texas Dallas, Richardson, TX 75080 USA
2.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing 100050, Peoples R China
3.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China
4.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
5.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
6.Novo Nordisk AS, Oral Formulat Dev, DK-2760 Malov, Denmark
7.Univ Copenhagen, Fac Hlth & Med Sci, Dept Pharm, DK-2100 Copenhagen, Denmark
推荐引用方式
GB/T 7714		 Li, Jingyi,Zhang, Yaqi,Yu, Miaorong,et al. The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery[J]. ACTA PHARMACEUTICA SINICA B,2022,12(3):1460-1472.
APA Li, Jingyi.,Zhang, Yaqi.,Yu, Miaorong.,Wang, Aohua.,Qiu, Yu.,...&Gan, Yong.(2022).The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery.ACTA PHARMACEUTICA SINICA B,12(3),1460-1472.
MLA Li, Jingyi,et al."The upregulated intestinal folate transporters direct the uptake of ligand-modified nanoparticles for enhanced oral insulin delivery".ACTA PHARMACEUTICA SINICA B 12.3(2022):1460-1472.

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来源：上海药物研究所

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