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Akkermansia Muciniphila-Inspired Oral siRNA Delivery by Active Matrix-Penetration and Intracellular Endoplasmic Reticulum Accumulation

文献类型：期刊论文

作者Pan, Chao1,2,3; Wang, Yang1,2,4; Zhang, Min1,2,3,5; Zhou, Taotao1,2,6; Ye, Liqin1,2,4; Tang, Fenqing1,2,4; Liu, Hongyu1,2,6; Yan, Yuzhong9; Gan, Yong1,2,3,7,8,9
刊名ADVANCED MATERIALS
出版日期2025-11-18
页码16
关键词Akkermansia muciniphila bacterial vesicles endoplasmic reticulum matrix-penetration siRNA delivery
ISSN号0935-9648
DOI10.1002/adma.202515901
英文摘要Oral delivery of small interfering ribonucleic acid (siRNA) is highly challenging due to the multiple barriers present in the gastrointestinal tract and within cells. Herein, inspired by intestinal Akkermansia muciniphila, the use of Akkermansia muciniphila membrane vesicles (AMVs) is introduced as an effective tool for oral delivery of siRNA. It is revealed that, distinct from common passive mucus-penetrating nanoparticles, AMVs enable active mucus penetration by degrading intestinal mucins, thereby enhancing their ability to traverse the intestinal barrier by approximately 4.6 times. Additionally, AMVs can markedly heighten siRNA penetration into tumor tissues. Once inside tumor cells, AMVs bypass the traditional endosomal-lysosomal degradation pathway typical of lipid-based delivery systems. Instead, they utilize a rapid transport expressway from the Golgi apparatus to the endoplasmic reticulum (ER), facilitating the accumulation of siRNA within the ER and thereby markedly enhancing gene silencing efficiency. In a mouse model of colorectal cancer, this formulation effectively inhibits tumor growth by 91.6%, and it exhibits a favorable biosafety profile. Overall, this research unveils a unique and promising bioinspired platform for oral siRNA delivery, advancing the development of safe and efficient oral nucleic acid therapeutics.
WOS关键词PD-L1 SIRNA ; INHIBITION ; MUCUS
资助项目Shanghai Action Plan for Science, Technology and Innovation[23HC1401200] ; Shanghai Municipal Science and Technology Major Project ; Research Grant for Pudong Health Bureau of Shanghai[PW2024D-10] ; Shanghai Postdoctoral Excellence Program[2021427] ; Shanghai Postdoctoral Excellence Program[2021430] ; Strategic Priority Research Program of the Chinese Academy of Sciences[XDB0830000] ; Open Competition to Select the Best Candidates Key Technology Program for Nucleic Acid Drugs of NCTIB[NCTIB2022HS01006] ; Science and Technology Commission of Pudong New Area of Shanghai[PKJ2023-Y109] ; China National Postdoctoral Program for Innovative Talents[BX20220322] ; The construction project of Shanghai Key Laboratory of Molecular Imaging[18DZ2260400] ; National Natural Science Foundation of China[82025032] ; National Natural Science Foundation of China[82430111] ; National Natural Science Foundation of China[52503214] ; Self Designed Scientific Research of Shanghai Institute of Materia Medica, Chinese Academy of Sciences[SIMM0220232001] ; China Post-doctoral Science Foundation[2021M703350] ; China Post-doctoral Science Foundation[2021M703354]
WOS研究方向Chemistry ; Science & Technology - Other Topics ; Materials Science ; Physics
语种英语
WOS记录号WOS:001616513900001
出版者WILEY-V C H VERLAG GMBH
源URL[http://119.78.100.183/handle/2S10ELR8/321977]  
专题国家级研究中心_原创新药研究全国重点实验室
通讯作者Yan, Yuzhong; Gan, Yong
作者单位1.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China
2.Chinese Acad Sci, Shanghai Inst Mat Med, Ctr Pharmaceut, Shanghai 201203, Peoples R China
3.Univ Chinese Acad Sci, Beijing 100049, Peoples R China
4.Henan Univ, Sch Pharm, Kaifeng 475004, Peoples R China
5.Shanghai Ocean Univ, Dept Biopharmaceut Sci, Shanghai 201306, Peoples R China
6.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, Peoples R China
7.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Beijing 102629, Peoples R China
8.Shenyang Pharmaceut Univ, Sch Pharm, Shenyang 110016, Peoples R China
9.Shanghai Univ Med & Hlth Sci, Zhoupu Hosp, Shanghai Key Lab Mol Imaging, Shanghai 200237, Peoples R China
推荐引用方式
GB/T 7714		 Pan, Chao,Wang, Yang,Zhang, Min,et al. Akkermansia Muciniphila-Inspired Oral siRNA Delivery by Active Matrix-Penetration and Intracellular Endoplasmic Reticulum Accumulation[J]. ADVANCED MATERIALS,2025:16.
APA Pan, Chao.,Wang, Yang.,Zhang, Min.,Zhou, Taotao.,Ye, Liqin.,...&Gan, Yong.(2025).Akkermansia Muciniphila-Inspired Oral siRNA Delivery by Active Matrix-Penetration and Intracellular Endoplasmic Reticulum Accumulation.ADVANCED MATERIALS,16.
MLA Pan, Chao,et al."Akkermansia Muciniphila-Inspired Oral siRNA Delivery by Active Matrix-Penetration and Intracellular Endoplasmic Reticulum Accumulation".ADVANCED MATERIALS (2025):16.

入库方式： OAI收割

来源：上海药物研究所

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