Hong, Kyung Tae Park, Seung Bin Murale, Dhiraj P. Hoon Lee, Jung Hwang, Jangsun Young Jang, Woo Lee, Jun-Seok 2024-05-23T07:00:25Z 2024-05-23T07:00:25Z 2024-05-23 2024-06 1433-7851 https://pubs.kist.re.kr/handle/201004/149893 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. First disaggregation induced pan-COX imaging agents shed light on cancer stem cells in human sarcoma tissue. Using the pan-COX targeting indomethacin conjugated BODIPY fluorophore, disaggregation dependent turn-on chemosensor was designed for parafin-fixed tissue imaging. Disaggregation schematics are created with BioRender.com image English John Wiley & Sons Ltd. Disaggregation-Activated pan-COX Imaging Agents for Human Soft tissue Sarcoma Article 10.1002/anie.202405525 1 Angewandte Chemie International Edition, v.63, no.24 Angewandte Chemie International Edition 63 24 Y scie scopus 001217348500001 2-s2.0-85192710780 Chemistry, Multidisciplinary Chemistry Article FLUORESCENT-PROBE CANCER CYCLOOXYGENASE-2 EXPRESSION CELLS TUMOR INFLAMMATION ROFECOXIB INVASION disaggregation BODIPY COX-2 Cancer Stem Cell chemosensor