pH-Activatable Molecular Probe for COX-2 Imaging in Human Oral Squamous Carcinoma Cells and Patient-Derived Tissues

ACS Appl Bio Mater. 2024 Dec 16;7(12):8517-8527. doi: 10.1021/acsabm.4c01323. Epub 2024 Nov 19.

Abstract

For developing a successful cancer therapeutic modality, the early precise detection of cancer cells in patient biopsies in oral squamous cell carcinoma (OSCC) is crucial. This could help researchers create new diagnostic and therapeutic tools and assist clinicians in recommending more effective treatment plans and improving patient survival. We have developed an SMPD, cyclooxygenase-2 (COX-2) targeting pH-activable fluorophore named CNP, combining a potent COX-2 inhibitor, celecoxib, linked to a naphthalimide fluorophore with an acidic microenvironment-responsive piperazine moiety for specific optical imaging of OSCC in cells and patient tissues. Compared to reference probe RNP lacking celecoxib, CNP selectively enters the COX-2 overexpressing oral cancer cells. Its acidity-responsive imaging response enhances selectivity over cancers with lower COX-2 expression levels and normal cells. Further, CNP is demonstrated in imaging OSCC cells in patient-derived biopsies. Thus, multifunctional CNP shows potential in exploring more reagents for fluorescence-based detection of OSCC cells in patient tissues with translational applications.

Keywords: cancer imaging; oral squamous cell carcinoma (OSCC); patient biopsy; small molecular probe for diagnosis (SMPD); tumor acidity.

MeSH terms

  • Biocompatible Materials / chemical synthesis
  • Biocompatible Materials / chemistry
  • Biocompatible Materials / pharmacology
  • Carcinoma, Squamous Cell* / diagnostic imaging
  • Carcinoma, Squamous Cell* / pathology
  • Celecoxib / chemistry
  • Celecoxib / pharmacology
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyclooxygenase 2* / metabolism
  • Fluorescent Dyes / chemical synthesis
  • Fluorescent Dyes / chemistry
  • Humans
  • Hydrogen-Ion Concentration
  • Materials Testing
  • Molecular Probes / chemistry
  • Molecular Structure
  • Mouth Neoplasms* / diagnostic imaging
  • Mouth Neoplasms* / metabolism
  • Mouth Neoplasms* / pathology
  • Optical Imaging*
  • Particle Size

Substances

  • Cyclooxygenase 2
  • Biocompatible Materials
  • Fluorescent Dyes
  • Molecular Probes
  • Celecoxib
  • Cyclooxygenase 2 Inhibitors
  • PTGS2 protein, human