한빛사논문
- 조회95
Hochung Jang1,2, Jiwoong Choi1, Daeho Park1,3, Geonhee Han1,5, Eun Hye Kim1,3, Kwangmeyung Kim4, Sun Hwa Kim1,5, Man Kyu Shim1,*, Yoosoo Yang1,2,*
1Medicinal Materials Research Center, Biomedical Research Division, Korea Institute of Science and Technology (KIST), Seoul, 02792, Republic of Korea.
2Division of Bio-Medical Science and Technology, KIST School, Korea University of Science and Technology, Seoul 02792, Republic of Korea.
3Department of Life Sciences, Korea University, Seoul, 02841, Republic of Korea.
4College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul 03760, Republic of Korea.
5KU-KIST Graduate School of Converging Science and Technology, Korea University, Seoul, 02841, Republic of Korea.
*Corresponding authors: Yoosoo Yang and Man Kyu Shim
Abstract
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.
Methods: 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.
Results: 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.
Conclusions: 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.
논문정보
- Research article
- 2024년 08월 (BRIC 등록일 2024-08-30)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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