Enzymatic Self-Immobilization Enhances Chemiluminescence for Selective Tumor Imaging and Image-Guided Surgery

Area of Science:

• Biomedical Engineering
• Chemical Biology
• Molecular Imaging

Background:

• Enzyme-activated chemiluminescence offers high specificity and sensitivity for bioimaging.
• Current chemiluminophores struggle with low light emission and poor water solubility for in vivo applications.
• Tracking analytes in living cells and tumors remains challenging due to these limitations.

Purpose of the Study:

• To develop an enzyme-triggered self-immobilizing strategy to enhance chemiluminescence for in vivo bioimaging.
• To create a probe for rapid tumor imaging and image-guided tumor surgery.
• To overcome limitations of insufficient light emission and low water solubility in current chemiluminophores.

Main Methods:

• Designed a probe with an ortho-fluoromethyl motif linked to a galactose recognition site and a chemiluminescent unit.
• Utilized beta-galactosidase activation leading to self-immolation cleavage and generation of an ortho-quinone methide species.
• Demonstrated probe activation and chemiluminescence enhancement in HepG2 liver tumor cells and xenografts.

Main Results:

• Achieved an 8900-fold chemiluminescence enhancement with a signal-to-noise ratio over 3220.
• Observed rapid and selective chemiluminescence increase in beta-galactosidase-overexpressing HepG2 cells.
• Successfully demonstrated immediate, bright, and long-lasting chemiluminescence in vivo, enabling image-guided tumor surgery in mice.

Conclusions:

• The enzyme-triggered self-immobilizing scaffold provides enhanced turn-on chemiluminescence for in vitro and in vivo imaging.
• This versatile agent facilitates image-guided tumor surgery and opens possibilities for biological sensing and therapeutics.
• The strategy significantly improves chemiluminescence for cancer cell and tumor detection.