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Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy

文献类型：期刊论文

作者Yang, Tiantian2,3; Wang, Aohua2,3; Nie, Di2,3; Fan, Weiwei2,3; Jiang, Xiaohe2,3; Yu, Miaorong2,3; Guo, Shiyan3; Zhu, Chunliu3; Wei, Gang1; Gan, Yong2,3,4
刊名NATURE COMMUNICATIONS
出版日期2022-11-04
卷号13期号:1页码:16
DOI10.1038/s41467-022-34357-8
通讯作者Wei, Gang(weigang@shmu.edu.cn) ; Gan, Yong(ygan@simm.ac.cn)
英文摘要Mutual interference between surface ligands on multifunctional nanoparticles remains a significant obstacle to achieving optimal drug-delivery efficacy. Here, we develop ligand-switchable nanoparticles which resemble viral unique surfaces, enabling them to fully display diverse functions. The nanoparticles are modified with a pH-responsive stretchable cell-penetrating peptide (Pep) and a liver-targeting moiety (Gal) (Pep/Gal-PNPs). Once orally administered, the acidic environments trigger the extension of Pep from surface in a virus-like manner, enabling Pep/Gal-PNPs to traverse intestinal barriers efficiently. Subsequently, Gal is exposed by Pep folding at physiological pH, thereby allowing the specific targeting of Pep/Gal-PNPs to the liver. As a proof-of-concept, insulin-loaded Pep/Gal-PNPs are fabricated which exhibit effective intestinal absorption and excellent hepatic deposition of insulin. Crucially, Pep/Gal-PNPs increase hepatic glycogen production by 7.2-fold, contributing to the maintenance of glucose homeostasis for effective diabetes management. Overall, this study provides a promising approach to achieving full potential of diverse ligands on multifunctional nanoparticles. Displaying the correct surface functionality at the right time is important for efficient drug delivery. Here, the authors report on the pH-responsive, sequential presentation of cell-penetrating peptide and liver-targeting moiety designed to improve intestinal absorption and liver targeting and demonstrate this with insulin delivery in vivo.
WOS关键词CELL-PENETRATING PEPTIDE ; POLYMERIC MICELLES ; HEPATIC GLYCOGEN ; NANOCARRIERS ; PACLITAXEL ; COPOLYMER ; OVERCOME ; LIVER ; PLGA
资助项目National Science Fund of Distinguished Young Scholars[82025032] ; National Natural Science Foundation of China[82003678] ; National Natural Science Foundation of China[82073773] ; Major International Joint Research Project of Chinese Academy of Sciences[153631KYSB20190020] ; Fudan-SIMM Joint Research Fund[FU-SIMM 20173006] ; Chinese Pharmacopoeia Commission[2021Y20]
WOS研究方向Science & Technology - Other Topics
语种英语
WOS记录号WOS:000879110700020
出版者NATURE PORTFOLIO
源URL[http://119.78.100.183/handle/2S10ELR8/304428]  
专题新药研究国家重点实验室
通讯作者Wei, Gang; Gan, Yong
作者单位1.Fudan Univ, Sch Pharm, Dept Pharmaceut, Minist Educ,Key Lab Smart Drug Delivery, Shanghai 201203, Peoples R China
2.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
3.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
4.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipi, Beijing 100050, Peoples R China
推荐引用方式
GB/T 7714		 Yang, Tiantian,Wang, Aohua,Nie, Di,et al. Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy[J]. NATURE COMMUNICATIONS,2022,13(1):16.
APA Yang, Tiantian.,Wang, Aohua.,Nie, Di.,Fan, Weiwei.,Jiang, Xiaohe.,...&Gan, Yong.(2022).Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy.NATURE COMMUNICATIONS,13(1),16.
MLA Yang, Tiantian,et al."Ligand-switchable nanoparticles resembling viral surface for sequential drug delivery and improved oral insulin therapy".NATURE COMMUNICATIONS 13.1(2022):16.

入库方式： OAI收割

来源：上海药物研究所

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