박승빈 (고려대학교 의과대학, 약리학교실)

한빛사논문

조회536

박승빈Seung Bin Park

고려대학교 의과대학, 약리학교실

CV File 495 kb

Angew. Chem.-Int. Edit., Apr 12 2024, | https://doi.org/10.1002/anie.202405525 Disaggregation-Activated pan-COX Imaging Agents for Human Soft Tissue Sarcoma

Kyung Tae Hong^,a,b,‡ Seung Bin Park,^c,‡ Dhiraj P. Murale,^b,‡ Jung Hoon Lee,^c Jangsun Hwang,^dWoo Young Jang,^d,* Jun-Seok Lee^c,*

^aBio-Med Program, KIST-School UST, Hwarang-ro 14 gil 5, Seongbuk-gu, Seoul 02792, South Korea

^bBio-Med Chemical & Biological Integrative Research Center, KIST, Hwarang-ro 14 gil 5, Seongbuk-gu,Seoul02792, South Korea

^cDepartment of Pharmacology, Korea University73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, South Korea

^dDepartment of Orthopedic Surgery, Korea University College of Medicine, 73 Goryeodae-ro, Seongbuk-gu, Seoul 02841, South Korea

^‡Footnote, e.g.: These authors contributed equally to this work.

^*CORRESPONDING AUTHORS: Jun-Seok Lee, Woo Young Jang

Abstract

Cancer stem cells are pivotal players in tumors initiation, growth, and metastasis. While several markers have been identified, there remain challenges particularly in heterogeneous malignancies like adult soft tissue sarcomas, where conventional markers are inherently overexpressed. Here, we designed BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) that activate via disaggregation targeting for cyclooxygenase (COX), a potential marker for CSCs in sarcoma in clinical pathology. Based on their structures, BD-IMC-1 showcased higher susceptibility to disaggregation compared to BD-IMC-2, consistent with their selective interaction with COX. Notably, the BD-IMC-1 revealed positive cooperativity binding to COX-2 at sub-micromolar ranges. Both probes showed significant fluorescence turn-on upon LPS or PMA triggered COX-2 upregulation in live RAW264.7, HeLa, and human sarcoma cell line (Saos-LM2) up to 2-fold increase with negligible toxicity. More importantly, the BD-IMC-1 demonstrated their practical imaging for COX-2 positive cells in paraffin-fixed human sarcoma tissue. Considering the fixed tissues are most practiced pathological sample, our finding suggests a potential of disaggregation activated chemosensor for clinical applications.

논문정보

형식Research article
게재일2024년 04월 (BRIC 등록일 2024-04-15)
연구진국내 연구진
분야 생명과학 > 생화학

댓글 작성 로그인

CV 열람하기

연락처 보기