Hochung Jang, Jiwoong Choi, Daeho Park, Geonhee Han, Eun Hye Kim, Kwangmeyung Kim, Sun Hwa Kim, Man Kyu Shim, Yoosoo Yang
{"title":"源于牛奶的细胞外囊泡实现了从肠道到肿瘤的肿瘤活性多柔比星原药口服递送","authors":"Hochung Jang, Jiwoong Choi, Daeho Park, Geonhee Han, Eun Hye Kim, Kwangmeyung Kim, Sun Hwa Kim, Man Kyu Shim, Yoosoo Yang","doi":"10.7150/thno.97269","DOIUrl":null,"url":null,"abstract":"<b>Rationale:</b> Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Despite the current advancements in nanoparticle-mediated drug delivery, numerous anticancer drugs susceptible to the hostile gastrointestinal (GI) environment exhibit poor permeability across the intestinal epithelium, rendering them ineffective in providing therapeutic benefits. In this paper, we focus on harnessing milk-derived extracellular vesicles (mEVs) for gut-to-tumor oral drug delivery by leveraging their high bioavailability./n<b>Methods:</b> The tumor-activated prodrug (a cathepsin B-specific cleavable FRRG peptide and doxorubicin, FDX) is used as a model drug and is complexed with mEVs, resulting in FDX@mEVs. To verify stability in the GI tract, prolonged intestinal retention, and enhanced trans-epithelial transport via neonatal Fc receptor (FcRn)-mediated transcytosis, intestinal transport evaluation is conducted using <i>in vitro</i> intestinal barrier model and mouse model./n<b>Results</b>: FDX@mEVs form a stable nanostructure with an average diameter of 131.1 ± 70.5 nm and complexation processes do not affect the inherent properties of FDX. Orally administered FDX@mEVs show significantly improved bioavailability compared to uncomplexed FDX via FcRn-mediated transcytosis of mEVs resulting in increased tumor accumulation of FDX in tumor-bearing mouse model./n<b>Conclusions:</b> After oral administration of FDX@mEVs, it is observed that remarkable antitumor efficacy in colon tumor-bearing mice without adverse effects, such as body weight loss, liver/kidney dysfunction, and cardiotoxicity.","PeriodicalId":22932,"journal":{"name":"Theranostics","volume":null,"pages":null},"PeriodicalIF":12.4000,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Milk-derived extracellular vesicles enable gut-to-tumor oral delivery of tumor-activated doxorubicin prodrugs\",\"authors\":\"Hochung Jang, Jiwoong Choi, Daeho Park, Geonhee Han, Eun Hye Kim, Kwangmeyung Kim, Sun Hwa Kim, Man Kyu Shim, Yoosoo Yang\",\"doi\":\"10.7150/thno.97269\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<b>Rationale:</b> Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Despite the current advancements in nanoparticle-mediated drug delivery, numerous anticancer drugs susceptible to the hostile gastrointestinal (GI) environment exhibit poor permeability across the intestinal epithelium, rendering them ineffective in providing therapeutic benefits. In this paper, we focus on harnessing milk-derived extracellular vesicles (mEVs) for gut-to-tumor oral drug delivery by leveraging their high bioavailability./n<b>Methods:</b> The tumor-activated prodrug (a cathepsin B-specific cleavable FRRG peptide and doxorubicin, FDX) is used as a model drug and is complexed with mEVs, resulting in FDX@mEVs. To verify stability in the GI tract, prolonged intestinal retention, and enhanced trans-epithelial transport via neonatal Fc receptor (FcRn)-mediated transcytosis, intestinal transport evaluation is conducted using <i>in vitro</i> intestinal barrier model and mouse model./n<b>Results</b>: FDX@mEVs form a stable nanostructure with an average diameter of 131.1 ± 70.5 nm and complexation processes do not affect the inherent properties of FDX. Orally administered FDX@mEVs show significantly improved bioavailability compared to uncomplexed FDX via FcRn-mediated transcytosis of mEVs resulting in increased tumor accumulation of FDX in tumor-bearing mouse model./n<b>Conclusions:</b> After oral administration of FDX@mEVs, it is observed that remarkable antitumor efficacy in colon tumor-bearing mice without adverse effects, such as body weight loss, liver/kidney dysfunction, and cardiotoxicity.\",\"PeriodicalId\":22932,\"journal\":{\"name\":\"Theranostics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":12.4000,\"publicationDate\":\"2024-08-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Theranostics\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.7150/thno.97269\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MEDICINE, RESEARCH & EXPERIMENTAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Theranostics","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.7150/thno.97269","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MEDICINE, RESEARCH & EXPERIMENTAL","Score":null,"Total":0}
Rationale: Oral chemotherapy has been emerging as a hopeful therapeutic regimen for the treatment of various cancers because of its high safety and convenience, lower costs, and high patient compliance. Despite the current advancements in nanoparticle-mediated drug delivery, numerous anticancer drugs susceptible to the hostile gastrointestinal (GI) environment exhibit poor permeability across the intestinal epithelium, rendering them ineffective in providing therapeutic benefits. In this paper, we focus on harnessing milk-derived extracellular vesicles (mEVs) for gut-to-tumor oral drug delivery by leveraging their high bioavailability./nMethods: The tumor-activated prodrug (a cathepsin B-specific cleavable FRRG peptide and doxorubicin, FDX) is used as a model drug and is complexed with mEVs, resulting in FDX@mEVs. To verify stability in the GI tract, prolonged intestinal retention, and enhanced trans-epithelial transport via neonatal Fc receptor (FcRn)-mediated transcytosis, intestinal transport evaluation is conducted using in vitro intestinal barrier model and mouse model./nResults: FDX@mEVs form a stable nanostructure with an average diameter of 131.1 ± 70.5 nm and complexation processes do not affect the inherent properties of FDX. Orally administered FDX@mEVs show significantly improved bioavailability compared to uncomplexed FDX via FcRn-mediated transcytosis of mEVs resulting in increased tumor accumulation of FDX in tumor-bearing mouse model./nConclusions: After oral administration of FDX@mEVs, it is observed that remarkable antitumor efficacy in colon tumor-bearing mice without adverse effects, such as body weight loss, liver/kidney dysfunction, and cardiotoxicity.
期刊介绍:
Theranostics serves as a pivotal platform for the exchange of clinical and scientific insights within the diagnostic and therapeutic molecular and nanomedicine community, along with allied professions engaged in integrating molecular imaging and therapy. As a multidisciplinary journal, Theranostics showcases innovative research articles spanning fields such as in vitro diagnostics and prognostics, in vivo molecular imaging, molecular therapeutics, image-guided therapy, biosensor technology, nanobiosensors, bioelectronics, system biology, translational medicine, point-of-care applications, and personalized medicine. Encouraging a broad spectrum of biomedical research with potential theranostic applications, the journal rigorously peer-reviews primary research, alongside publishing reviews, news, and commentary that aim to bridge the gap between the laboratory, clinic, and biotechnology industries.