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Disaggregation-Activated pan-COX Imaging Agents for Human Soft tissue Sarcoma.

Kyung Tae Hong1,2, Seung Bin Park3, Dhiraj P Murale2

  • 1Bio-Med Program, KIST-School UST, Hwarang-ro 14 gil 5, Seongbuk-gu, Seoul, 02792, South Korea.

Angewandte Chemie (International Ed. in English)
|April 12, 2024
PubMed
Summary

New fluorescence probes target cyclooxygenase (COX) to identify cancer stem cells in sarcomas. This disaggregation-activated sensor shows promise for clinical pathology imaging of sarcoma tissues.

Keywords:
BODIPYCOX-2Cancer Stem Cellchemosensordisaggregation

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Area of Science:

  • Biomedical Engineering
  • Chemical Biology
  • Oncology

Background:

  • Cancer stem cells (CSCs) drive tumor initiation, growth, and metastasis.
  • Identifying CSCs in heterogeneous malignancies like soft tissue sarcomas is challenging due to conventional marker overexpression.
  • Cyclooxygenase (COX) is a potential CSC marker in sarcoma, but requires specific detection methods.

Purpose of the Study:

  • To design and synthesize novel BODIPY-based fluorescence probes (BD-IMC-1, BD-IMC-2) for detecting cyclooxygenase (COX).
  • To evaluate the probes' ability to target and image CSCs in sarcoma, particularly COX-2 positive cells.
  • To assess the probes' potential for clinical pathological applications in fixed human sarcoma tissues.

Main Methods:

  • Synthesis of BODIPY scaffold fluorescence probes (BD-IMC-1, BD-IMC-2) designed for disaggregation activation.
  • Assessment of probe disaggregation susceptibility and selective interaction with COX enzymes.
  • Evaluation of probe fluorescence turn-on response to COX-2 upregulation in live cell lines (RAW264.7, HeLa, Saos-LM2) and fixed human sarcoma tissues.
  • Toxicity assessment of the probes.

Main Results:

  • BD-IMC-1 exhibited higher disaggregation susceptibility and selective interaction with COX compared to BD-IMC-2.
  • BD-IMC-1 demonstrated positive cooperative binding to COX-2 at sub-micromolar concentrations.
  • Both probes showed a significant fluorescence 'turn-on' (up to 2-fold increase) in live cells with upregulated COX-2, with negligible toxicity.
  • BD-IMC-1 successfully imaged COX-2 positive cells in paraffin-fixed human sarcoma tissue.

Conclusions:

  • Disaggregation-activated fluorescent probes, specifically BD-IMC-1, can effectively target and image COX-2 in live cells and fixed sarcoma tissues.
  • These probes offer a sensitive and selective method for identifying potential cancer stem cells in clinical pathology.
  • The developed chemosensors hold significant potential for advancing diagnostic applications in sarcoma research and clinical practice.