한빛사논문
Ryunhyung Kim1, Byeonggeol Mun1, Jaewoo Lim2,3, Hyein Jeong1, Hye Young Son4,5, Byunghoon Kang3,6, Seongjae Lim1, Minkyung Kang1, Hyun Wook Rho4, Yong-min Huh4,5,7, Seung Jae Oh5, Jaewook Lim1, Eun-Kyung Lim3,8,9*, Seungjoo Haam1*
1Department of Chemical and Biomolecular Engineering, College of Engineering, Yonsei University, Seoul, 03722 Republic of Korea
2Medical Device Development Center, Osong Medical Innovation Foundation, Daejeon, 28160 Republic of Korea
3Bionanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB), Daejeon, 34141 Republic of Korea
4Department of Radiology, College of Medicine, Yonsei University, Seoul, 03722 South Korea
5YUHS-KRIBB Medical Convergence Research Institute, College of Medicine, Yonsei University, Seoul, 03722 South Korea
6Genetics and Aging Research Unit, McCance Center for Brain Health, Mass General Institute for Neurodegenerative Disease (MIND), Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, 02129 USA
7Department of Biochemistry & Molecular Biology, College of Medicine, Yonsei University, Seoul, 03722 South Korea
8Department of Nanobiotechnology, KRIBB School of Biotechnology, University of Science and Technology, Daejeon, 34113 Republic of Korea
9School of Pharmacy, Sungkyunkwan University, Suwon, Gyeonggi-do, 16419 Republic of Korea
*Corresponding Authors: Eun-Kyung Lim, Seungjoo Haam
Abstract
Point-of-care (POC) monitoring of patient condition is crucial for effective cancer treatment and prognosis. This can be achieved non-invasively by analyzing exosomes in body fluids. However, the heterogeneity of exosomes and non-standardized quantification methods may interfere with clearly determining the patient's condition. Therefore, there is a need for technology that can precisely analyze both tumor-derived exosomes and normal exosomes. Herein, this study presents the exosome multiple-separation for simultaneous detection (EXO-MUSSID) platform, which simultaneously isolates different exosomes based on their magnetization properties and monitors therapeutic efficacy of drugs. Using immunoaffinity magnetophoresis technology, HER2-overexpressing and normal exosomes are collected separately, enabling real-time monitoring of HER2 (also known as ERBB2) expression by analyzing the mRNA of each exosome based on a catalytic hairpin assembly (CHA) reaction. A portable fluorescence reader customized for the EXO-MUSSID platform is developed for POC monitoring of HER2-overexpressing breast cancer (HER2+ BC). The performance of the EXO-MUSSID platform is validated using urine samples from HER2+ BC mouse models, confirming the progression of HER2+ BC and the changes in HER2 expression due to trastuzumab treatment. It is expected to serve as a valuable tool for exosome-based liquid biopsy in disease monitoring.
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