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ACS Nano, Sep 09 2024, | https://doi.org/10.1021/acsnano.4c08339 All-in-One Fusogenic Nanoreactor for the Rapid Detection of Exosomal MicroRNAs for Breast Cancer Diagnosis

Chaewon Park ^1‡‡, Soohyun Chung ^1‡‡, Hansol Kim ¹, Nayoung Kim ^2,3,4, Hye Young Son ^5,6, Ryunhyung Kim ¹, Sojeong Lee ¹, Geunseon Park¹, Hyun Wook Rho ⁵, Mirae Park ⁵, Jueun Han ⁷, Yejin Song ⁷, Jihee Lee ⁸, Sung-Hoon Jun ⁹, Yong-Min Huh ^5,6, Hyoung Hwa Jeong ¹⁰, Eun-Kyung Lim^11,12,13*, Eunjung Kim ^7,8*, Seungjoo Haam^1*

¹Department of Chemical and Biomolecular Engineering, Yonsei University, Seoul 03722, Republic of Korea.

²Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, Massachusetts 02115, United States.

³Department of Biological Engineering, Massachusetts Institute of Technology (MIT), Cambridge, Massachusetts 02139, United States.

⁴Institute for Medical Engineering and Science, MIT, Cambridge, Massachusetts 02139, United States.

⁵Department of Radiology, College of Medicine, Yonsei University, Seoul 03722, Republic of Korea.

⁶YUHS-KRIBB Medical Convergence Research Institute, Seoul 03722, Republic of Korea.

⁷Department of Bioengineering and Nano-Bioengineering, Research Center for Bio Materials and Process Development, Incheon National University, Incheon 22012, Republic of Korea.

⁸Division of Bioengineering, Incheon National University, Incheon 22012, Republic of Korea.

⁹Electron Microscopy & Spectroscopy Team, Korea Basic Science Institute, Chungbuk 28119, Republic of Korea.

¹⁰Huvet Bio Inc., 127 Beobwon-ro, Seoul 05836, Republic of Korea.

¹¹BioNanotechnology Research Center, Korea Research Institute of Bioscience and Biotechnology(KRIBB), Daejeon 34141, Republic of Korea.

¹²Department of Nanobiotechnology, KRIBB School of Biotechnology, University of Science and Technology (UST), Daejeon 34113, Republic of Korea.

¹³School of Pharmacy, Sungkyunkwan University, Suwon 16419, Republic of Korea.

^‡‡C.P. and S.C. contributed equally to this work.

^*Corresponding authors: Eun-Kyung Lim, Eunjung Kim, Seungjoo Haam

Abstract

Molecular-profiling-based cancer diagnosis has significant implications for predicting disease prognosis and selecting targeted therapeutic interventions. The analysis of cancer-derived extracellular vesicles (EVs) provides a noninvasive and sequential method to assess the molecular landscape of cancer. Here, we developed an all-in-one fusogenic nanoreactor (FNR) encapsulating DNA-fueled molecular machines (DMMs) for the rapid and direct detection of EV-associated microRNAs (EV miRNAs) in a single step. This platform was strategically designed to interact selectively with EVs and induce membrane fusion under a specific trigger. After fusion, the DMMs recognized the target miRNA and initiated nonenzymatic signal amplification within a well-defined reaction volume, thus producing an amplified fluorescent signal within 30 min. We used the FNRs to analyze the unique expression levels of three EV miRNAs in various biofluids, including cell culture, urine, and plasma, and obtained an accuracy of 86.7% in the classification of three major breast cancer (BC) cell lines and a diagnostic accuracy of 86.4% in the distinction between patients with cancer and healthy donors. Notably, a linear discriminant analysis revealed that increasing the number of miRNAs from one to three improved the accuracy of BC patient discrimination from 78.8 to 95.4%. Therefore, this all-in-one diagnostic platform performs nondestructive EV processing and signal amplification in one step, providing a straightforward, accurate, and effective individual EV miRNA analysis strategy for personalized BC treatment.

논문정보

형식Research article
게재일2024년 09월 (BRIC 등록일 2024-09-11)
연구진국내(교신)+국외 연구진
분야 바이오·의료융합 > 바이오센싱 및 나노바이오물질

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