Toma Shinkai, Koki Ogawa, Tatsuaki Tagami, Tetsuya Ozeki
{"title":"胆酸介导的 mRNA 靶向-LNPs 可改善 mRNA 向 Caco-2 细胞的传递","authors":"Toma Shinkai, Koki Ogawa, Tatsuaki Tagami, Tetsuya Ozeki","doi":"10.1007/s11051-024-06161-6","DOIUrl":null,"url":null,"abstract":"<div><p>Oral administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is challenging due to various factors, including the low efficiency of mRNA-LNP uptake by small intestinal epithelial cells due to the low levels of apolipoprotein-E in gastrointestinal fluid. Therefore, in this study, we aimed to improve mRNA-LNP uptake by intestinal cells by modifying the surface of mRNA-LNPs with bile acids. Bile acids are recognized by bile acid transporters in the small intestine. We synthesized a polyethylene glycol (PEG)-lipid bound to cholic acid, a type of bile acid, and prepared cholic acid-modified mRNA-LNPs (Cholic-PEG-LNPs) using an ethanol dilution method with a microfluidic device. Uptake of Cholic-PEG-LNPs by differentiated Caco-2 cells was higher than that of unmodified PEG-LNPs. Moreover, protein expression induced by Cholic-PEG-LNPs was higher than that induced by unmodified PEG-LNPs in differentiated Caco-2 cells, and no difference was observed in bile acid transporter-negative MCF-7 cells. These results suggest that the cholic acid modification of mRNA-LNPs enhances bile acid transporter-mediated cellular uptake and protein expression. Our strategy can be used to enhance the functionality of oral mRNA-LNPs.</p><h3>Graphical Abstract</h3>\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>","PeriodicalId":653,"journal":{"name":"Journal of Nanoparticle Research","volume":"26 11","pages":""},"PeriodicalIF":2.1000,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Cholic acid-mediated targeting of mRNA-LNPs improve the mRNA delivery to Caco-2 cells\",\"authors\":\"Toma Shinkai, Koki Ogawa, Tatsuaki Tagami, Tetsuya Ozeki\",\"doi\":\"10.1007/s11051-024-06161-6\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Oral administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is challenging due to various factors, including the low efficiency of mRNA-LNP uptake by small intestinal epithelial cells due to the low levels of apolipoprotein-E in gastrointestinal fluid. Therefore, in this study, we aimed to improve mRNA-LNP uptake by intestinal cells by modifying the surface of mRNA-LNPs with bile acids. Bile acids are recognized by bile acid transporters in the small intestine. We synthesized a polyethylene glycol (PEG)-lipid bound to cholic acid, a type of bile acid, and prepared cholic acid-modified mRNA-LNPs (Cholic-PEG-LNPs) using an ethanol dilution method with a microfluidic device. Uptake of Cholic-PEG-LNPs by differentiated Caco-2 cells was higher than that of unmodified PEG-LNPs. Moreover, protein expression induced by Cholic-PEG-LNPs was higher than that induced by unmodified PEG-LNPs in differentiated Caco-2 cells, and no difference was observed in bile acid transporter-negative MCF-7 cells. These results suggest that the cholic acid modification of mRNA-LNPs enhances bile acid transporter-mediated cellular uptake and protein expression. Our strategy can be used to enhance the functionality of oral mRNA-LNPs.</p><h3>Graphical Abstract</h3>\\n<div><figure><div><div><picture><source><img></source></picture></div></div></figure></div></div>\",\"PeriodicalId\":653,\"journal\":{\"name\":\"Journal of Nanoparticle Research\",\"volume\":\"26 11\",\"pages\":\"\"},\"PeriodicalIF\":2.1000,\"publicationDate\":\"2024-11-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Nanoparticle Research\",\"FirstCategoryId\":\"88\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s11051-024-06161-6\",\"RegionNum\":4,\"RegionCategory\":\"材料科学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, MULTIDISCIPLINARY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Nanoparticle Research","FirstCategoryId":"88","ListUrlMain":"https://link.springer.com/article/10.1007/s11051-024-06161-6","RegionNum":4,"RegionCategory":"材料科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
Cholic acid-mediated targeting of mRNA-LNPs improve the mRNA delivery to Caco-2 cells
Oral administration of mRNA-encapsulated lipid nanoparticles (mRNA-LNPs) is challenging due to various factors, including the low efficiency of mRNA-LNP uptake by small intestinal epithelial cells due to the low levels of apolipoprotein-E in gastrointestinal fluid. Therefore, in this study, we aimed to improve mRNA-LNP uptake by intestinal cells by modifying the surface of mRNA-LNPs with bile acids. Bile acids are recognized by bile acid transporters in the small intestine. We synthesized a polyethylene glycol (PEG)-lipid bound to cholic acid, a type of bile acid, and prepared cholic acid-modified mRNA-LNPs (Cholic-PEG-LNPs) using an ethanol dilution method with a microfluidic device. Uptake of Cholic-PEG-LNPs by differentiated Caco-2 cells was higher than that of unmodified PEG-LNPs. Moreover, protein expression induced by Cholic-PEG-LNPs was higher than that induced by unmodified PEG-LNPs in differentiated Caco-2 cells, and no difference was observed in bile acid transporter-negative MCF-7 cells. These results suggest that the cholic acid modification of mRNA-LNPs enhances bile acid transporter-mediated cellular uptake and protein expression. Our strategy can be used to enhance the functionality of oral mRNA-LNPs.
期刊介绍：
The objective of the Journal of Nanoparticle Research is to disseminate knowledge of the physical, chemical and biological phenomena and processes in structures that have at least one lengthscale ranging from molecular to approximately 100 nm (or submicron in some situations), and exhibit improved and novel properties that are a direct result of their small size.
Nanoparticle research is a key component of nanoscience, nanoengineering and nanotechnology.
The focus of the Journal is on the specific concepts, properties, phenomena, and processes related to particles, tubes, layers, macromolecules, clusters and other finite structures of the nanoscale size range. Synthesis, assembly, transport, reactivity, and stability of such structures are considered. Development of in-situ and ex-situ instrumentation for characterization of nanoparticles and their interfaces should be based on new principles for probing properties and phenomena not well understood at the nanometer scale. Modeling and simulation may include atom-based quantum mechanics; molecular dynamics; single-particle, multi-body and continuum based models; fractals; other methods suitable for modeling particle synthesis, assembling and interaction processes. Realization and application of systems, structures and devices with novel functions obtained via precursor nanoparticles is emphasized. Approaches may include gas-, liquid-, solid-, and vacuum-based processes, size reduction, chemical- and bio-self assembly. Contributions include utilization of nanoparticle systems for enhancing a phenomenon or process and particle assembling into hierarchical structures, as well as formulation and the administration of drugs. Synergistic approaches originating from different disciplines and technologies, and interaction between the research providers and users in this field, are encouraged.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
