Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption
文献类型：期刊论文
| 作者 | Wang, Jie2,4; Zhang, Zilong2,4; Zhang, Zhuan3,4; Zou, Zhiwen4; Zhuo, Yan4; Liu, Chang4,5; Nie, Di4; Gan, Yong1,3,4,5 ; Yu, Miaorong4,5
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| 刊名 | ACS NANO
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| 出版日期 | 2024-12-16 |
| 卷号 | 18期号:52页码:35310-35324 |
| 关键词 | protein corona ligand-modified nanoparticles oral delivery liver targeting mucus |
| ISSN号 | 1936-0851 |
| DOI | 10.1021/acsnano.4c11453 |
| 通讯作者 | Gan, Yong(ygan@simm.ac.cn) ; Yu, Miaorong(mryu@simm.ac.cn) |
| 英文摘要 | The development of effective oral drug delivery systems for targeted gut-to-liver transport remains a significant challenge due to the multiple biological barriers including the harsh gastrointestinal tract (GIT) environment and the complex protein corona (PC) formation. In this study, we developed ligand-modified nanoparticles (NPs) that enable gut-to-liver drug delivery by crossing the GIT and attenuating PC formation. Specifically, mesoporous silica nanoparticles (MSNs) were functionalized with peptides targeting the neonatal Fc receptor (FcRn), capitalizing on FcRn expression in the small intestine and liver for targeted drug delivery. We showed that MSNs decorated with a small cyclic FcRn binding peptide (MSNs-FcBP) obtained enhanced diffusion in intestinal mucus and superior transportation across the intestine compared to unmodified MSNs and MSNs decorated with a large IgG Fc fragment (MSNs-Fc), which correlated with diminished protein adsorption and weaker interaction with mucin. After entering the blood circulation, reduced serum PC formation by MSNs-FcBP reduces the proteolytic and phagocytic propensity of the reticuloendothelial system, ultimately ameliorating accumulation in hepatocytes. Pharmacokinetic and pharmacodynamic studies in diabetic mice revealed that MSNs-FcBP effectively transported the therapeutic agent exenatide across the intestinal epithelium, leading to a significant hypoglycemic response and improved glucose tolerance. This study underscores the critical role of ligand selection in limiting protein corona formation, thereby significantly enhancing gut-to-liver drug delivery by increasing mucus permeation and minimizing serum-protein interactions. The effective delivery of exenatide in diabetic mice illustrates the potential of this strategy to optimize oral drug bioavailability and therapeutic efficacy. |
| WOS关键词 | NEONATAL FC-RECEPTOR ; PEPTIDE LIGAND ; TRANSCYTOSIS ; CELLS ; BARRIER |
| 资助项目 | China Association for Science and Technology[2024YFA1210100] ; National Key R&D Program of China[82025032] ; National Science Fund of Distinguished Young Scholars[82073773] ; National Science Fund of Distinguished Young Scholars[82304392] ; National Natural Science Foundation of China[ZDBS-ZRKJZ-TLC005] ; National Natural Science Foundation of China[NCTIB2022HS01006] ; Key Research Program of Chinese Academy of Sciences[2022QNRC001] ; Young Elite Scientists Sponsorship Program by CAST[23HC1401200] ; Shanghai Action Plan for Science, Technology[SIMM0220232001] ; Shanghai Institute of Materia Medica, Chinese Academy of Sciences ; Shanghai Advanced Research Institute, Chinese Academy of Sciences, China |
| WOS研究方向 | Chemistry ; Science & Technology - Other Topics ; Materials Science |
| 语种 | 英语 |
| WOS记录号 | WOS:001379339800001 |
| 出版者 | AMER CHEMICAL SOC |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/315163]  |
| 专题 | 中国科学院上海药物研究所 |
| 通讯作者 | Gan, Yong; Yu, Miaorong |
| 作者单位 | 1.Natl Inst Food & Drug Control, NMPA Key Lab Qual Res & Evaluat Pharmaceut Excipie, Beijing 100050, Peoples R China 2.Shanghai Univ Tradit Chinese Med, Sch Pharm, Shanghai 201203, Peoples R China 3.Nanjing Univ Chinese Med, Sch Chinese Mat Med, Nanjing 210023, 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 |
| 推荐引用方式 GB/T 7714 | Wang, Jie,Zhang, Zilong,Zhang, Zhuan,et al. Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption[J]. ACS NANO,2024,18(52):35310-35324. |
| APA | Wang, Jie.,Zhang, Zilong.,Zhang, Zhuan.,Zou, Zhiwen.,Zhuo, Yan.,...&Yu, Miaorong.(2024).Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption.ACS NANO,18(52),35310-35324. |
| MLA | Wang, Jie,et al."Enhanced Gut-to-Liver Oral Drug Delivery via Ligand-Modified Nanoparticles by Attenuating Protein Corona Adsorption".ACS NANO 18.52(2024):35310-35324. |
入库方式： OAI收割
来源：上海药物研究所
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