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ACS Nano, Mar 22 2025, | https://doi.org/10.1021/acsnano.4c15441
Modular and Nondisturbing Chimeric Adaptor Protein for Surface Chemistry of Small Extracellular Vesicles
Juhee Jang 1, Jiwon Shin 2, Yongdeok Ahn 1, Kiwook Kim 1, Juhyeong Cho 1, Wonhee John Lee 1, Chaerin Nam 2, Moon-Chang Baek 3, Daeha Seo 1, Kyungmoo Yea 2
1Department of Physics and Chemistry, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
2Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
3Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
J.J. and J.S. equally contributed.
Corresponding Authors : Moon-chang Baek, Daeha Seo, Kyungmoo Yea
1Department of Physics and Chemistry, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
2Department of New Biology, Daegu Gyeongbuk Institute of Science and Technology (DGIST), Daegu 42988, Republic of Korea.
3Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu 41944, Republic of Korea.
J.J. and J.S. equally contributed.
Corresponding Authors : Moon-chang Baek, Daeha Seo, Kyungmoo Yea
Abstract
Current chemical strategies for modifying the surface of extracellular vesicles (sEVs) often struggle to balance efficient functionalization with preserving structural integrity. Here, we present a modular approach for the surface modification of sEVs using a chimeric adaptor protein (CAP). The CAP was designed with three key features: a SNAP-tag for stable and modular binding, long and rigid linker to enhance spatial accessibility and conjugation efficiency, and the N-terminal sorting domain derived from syntenin to improve CAP expression on the sEV. We established a postsynthetic method to introduce diverse functional molecules onto sEVs, creating a versatile system termed "sEV-X" (where X represents an organic molecule, protein, or nanoparticle). Quantitative analyses at the single-molecule level revealed a linear relationship between CAP expression and the number of conjugated functional molecules, underscoring the importance of steric hindrance mitigation in sEV surface engineering. Moreover, antibody-conjugated sEVs as drug carriers, demonstrated significant tumor-specific delivery and therapeutic efficacy in a tumor-bearing mouse model, underscoring the potential of CAP-expressing sEVs as a customizable therapeutic vesicle. Overall, the CAP technology may serve as a universal platform for advancing the development of sEV-based therapeutics.
논문정보
- Research article
- 2025년 03월 (BRIC 등록일 2025-03-24)
- 국내 연구진
- 바이오·의료융합 > 바이오센싱 및 나노바이오물질
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