@article{8182d191d0f54784b21b729ba62d7709,
title = "A Noninvasive Gut-to-Brain Oral Drug Delivery System for Treating Brain Tumors",
abstract = "Most orally administered drugs fail to reach the intracerebral regions because of the intestinal epithelial barrier (IEB) and the blood–brain barrier (BBB), which are located between the gut and the brain. Herein, an oral prodrug delivery system that can overcome both the IEB and the BBB noninvasively is developed for treating gliomas. The prodrug is prepared by conjugating an anticancer drug on β-glucans using a disulfide-containing linker. Following oral administration in glioma-bearing mice, the as-prepared prodrug can specifically target intestinal M cells, transpass the IEB, and be phagocytosed/hitchhiked by local macrophages (Mϕ). The Mϕ-hitchhiked prodrug is transported to the circulatory system via the lymphatic system, crossing the BBB. The tumor-overexpressed glutathione then cleaves the disulfide bond within the prodrug, releasing the active drug, improving its therapeutic efficacy. These findings reveal that the developed prodrug may serve as a gut-to-brain oral drug delivery platform for the well-targeted treatment of gliomas.",
keywords = "blood–brain barrier, glioma, intestinal epithelial barrier, macrophage hitchhiking, prodrugs",
author = "Miao, {Yang Bao} and Chen, {Kuan Hung} and Chen, {Chiung Tong} and Mi, {Fwu Long} and Lin, {Yu Jung} and Yen Chang and Chiang, {Chi Shiun} and Wang, {Jui To} and Lin, {Kun Ju} and Sung, {Hsing Wen}",
note = "Funding Information: The authors would like to thank the Ministry of Science and Technology (109‐2124‐M‐007‐003 and 109‐2634‐F‐007‐023) and the Ministry of Education (Contract No. MOE 109QR001I5) of Taiwan, ROC for financially supporting this research. Animal experiments were carried out in accordance with the “Guide for the Care and Use of Laboratory Animals” that was prepared by the Institute of Laboratory Animal Resources, National Research Council, and published by the National Academy Press in 2011. The animal study protocols were approved by the Institutional Animal Care and Use Committee of National Tsing Hua University. Funding Information: The authors would like to thank the Ministry of Science and Technology (109-2124-M-007-003 and 109-2634-F-007-023) and the Ministry of Education (Contract No. MOE 109QR001I5) of Taiwan, ROC for financially supporting this research. Animal experiments were carried out in accordance with the ?Guide for the Care and Use of Laboratory Animals? that was prepared by the Institute of Laboratory Animal Resources, National Research Council, and published by the National Academy Press in 2011. The animal study protocols were approved by the Institutional Animal Care and Use Committee of National Tsing Hua University. Publisher Copyright: {\textcopyright} 2021 Wiley-VCH GmbH",
year = "2021",
month = aug,
day = "26",
doi = "10.1002/adma.202100701",
language = "English",
volume = "33",
journal = "Advanced Materials",
issn = "0935-9648",
publisher = "Wiley-Blackwell",
number = "34",
}