β-Galactosidase-Activated and Red Light-Induced RNA Modification Strategy for Prolonged NIR Fluorescence/PET...

Area of Science:

• Biomedical Imaging
• Molecular Imaging
• Cancer Therapy

Background:

• Effective tumor diagnosis and therapy require improved retention of small-molecule therapeutic agents.
• Current imaging techniques face challenges in achieving prolonged retention of agents within tumors.

Purpose of the Study:

• To develop a β-galactosidase (β-Gal)-activated and red light-induced RNA modification (GALIRM) strategy for prolonged tumor imaging.
• To create a bimodal probe for sensitive and long-term imaging of ovarian cancer.

Main Methods:

• Designed a β-Gal-activatable near-infrared fluorescence (NIR FL) and positron emission tomography (PET) bimodal probe (68Ga-NOTA-FCG).
• The probe incorporates a 68Ga chelator, a β-Gal-activated photosensitizer, and a furan group for RNA modification.
• Utilized β-Gal cleavage for NIR FL signal activation and 690 nm illumination for singlet oxygen generation and RNA cross-linking.

Main Results:

• The probe demonstrated activated NIR FL signal upon cleavage by endogenous β-Gal, enabling sensitive ovarian cancer imaging.
• Red light illumination triggered covalent cross-linking between the probe and cytoplasmic RNAs via singlet oxygen.
• This RNA cross-linking effectively prevented probe exocytosis, prolonging its retention in tumors.

Conclusions:

• The GALIRM strategy offers a novel approach for achieving prolonged probe retention in tumors.
• This method holds promise for advancing long-term tumor imaging and enhancing the efficiency of tumor treatment.
• The developed bimodal probe facilitates sensitive ovarian cancer detection and prolonged retention for therapeutic applications.