한빛사논문
- 조회242
Heejin Jun 1, Mirae Yeo 1, Jun Pyo Jeon 1, Soomin Eom, Hyo Jeong Kim, Yunjung Kim, Eunjung Jang, Sung Ho Park, Eunhee Kim, Sebyung Kang
Department of Biological Sciences, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, South Korea
1These authors contributed equally to this work.
Corresponding authors : Sung Ho Park, Eunhee Kim, Sebyung Kang
Abstract
Acute myeloid leukemia (AML) is a rapidly proliferating blood cancer, necessitating treatments that specifically target and swiftly eradicate it. In this study, we develop an AML-specific, apoptotic cell death-inducing protein nanoparticle, AaLS/TRAIL/aCD13Nb, by simultaneously displaying multiple CD13-binding nanobodies (aCD13Nb) and Tumor Necrosis Factor-Related Apoptosis-Inducing Ligand (TRAIL) molecules on a single AaLS protein nanoparticle using the SpyCatcher/SpyTag protein ligation system. AaLS/TRAIL/aCD13Nb selectively binds to various CD13-overexpressing AML cell lines and effectively accumulates near U937 AML tumor sites through systemic administration, demonstrating its AML targeting capabilities. The tight binding of AaLS/TRAIL/aCD13Nb to CD13-overexpressing AML cells, mediated by aCD13Nb, results in close and continuous contact between TRAIL molecules and death receptors, triggering robust apoptotic cell death. Systemic administrations of AaLS/TRAIL/aCD13Nb into U937 AML-engrafted NSG mice significantly reduce the AML burden and nearly double the mice’s survival period, especially under advanced and severe AML conditions. Collectively, our study paves the way for targeted therapies in AML, utilizing protein nanoparticles as nanoplatforms. Substantial therapeutic efficacy across various cancers can be achieved by strategically combining cancer-specific targeting ligands with apoptotic cancer cell death-inducing molecules, tailored to specific cancer types.
논문정보
- Research article
- 2024년 09월 (BRIC 등록일 2024-09-09)
- 국내 연구진
- 생명과학 > 생명과학 기타
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