One-Step Transformation from Rofecoxib to a COX-2 NIR Probe for Human Cancer Tissue/Organoid Targeted Bioimaging

Area of Science:

• Biomedical Engineering
• Molecular Imaging
• Chemical Biology

Background:

• Cyclooxygenase-2 (COX-2) plays a crucial role in cancer development and progression.
• Conventional fluorescent probes for COX-2 imaging often involve complex, multi-step synthesis.
• There is a need for efficient and sensitive COX-2 fluorescent probes for accurate cancer diagnosis.

Purpose of the Study:

• To develop a novel, simplified fluorescent probe for COX-2 imaging.
• To evaluate the COX-2 targeting ability and fluorescent properties of new rofecoxib analogues.
• To assess the potential of the developed probe for differentiating cancerous from non-cancerous human tissues.

Main Methods:

• A single-step synthetic strategy was employed to create six rofecoxib analogues.
• Fluorescent properties and COX-2 targeting activity were investigated experimentally and computationally.
• The most potent analogue, 2a1, was tested for COX-2 imaging in cell lines (HeLa, Raw 264.7) and human tissue samples (histological sections, 3D organoids).

Main Results:

• Six rofecoxib analogues were successfully synthesized with a single-step process.
• Several analogues demonstrated comparable COX-2 targeting and favorable fluorescent characteristics.
• The analogue 2a1 exhibited strong COX-2 specific fluorescence in HeLa cells overexpressing COX-2.
• 2a1 effectively distinguished human cancer tissue from adjacent normal tissue in histological sections and 3D organoids.

Conclusions:

• A facile single-step synthesis yielded potent COX-2 fluorescent probes.
• The analogue 2a1 shows significant promise as a near-infrared fluorescent probe for clinical human cancer imaging.
• This probe offers a potential advancement in sensitive and specific cancer diagnosis.