Photo-Generated ¹O₂ Triggers In Situ RNA Crosslinking for High-Contrast Tumor MRI and Effective Tumor Suppression

Area of Science:

• Biomedical Imaging
• Molecular Oncology
• Photodynamic Therapy

Background:

• Hepatocellular carcinoma (HCC) diagnosis and treatment face challenges due to poor contrast agent selectivity and lack of stable therapeutic targets.
• Existing imaging agents lack tumor specificity, and effective, broadly conserved therapeutic targets for HCC are absent.

Purpose of the Study:

• To develop a photoactivatable molecular probe for enhanced hepatocellular carcinoma (HCC) imaging and therapy.
• To exploit the RNA-rich nature of HCC for targeted imaging and treatment using a novel photoactivatable strategy.

Main Methods:

• Development of a photoactivatable molecular probe enabling combined magnetic resonance/fluorescence (MR/FL) imaging.
• Utilizing singlet oxygen (¹O₂) generated upon light irradiation to trigger in situ furan-RNA crosslinking.
• Evaluating the probe's performance in enhancing MR signal, tumor retention, and inducing synergistic antitumor effects.

Main Results:

• The probe achieved a 75% enhancement in tumor MR signal via light-activated RNA crosslinking, outperforming current agents.
• Fluorescence imaging demonstrated prolonged tumor retention (>14 days) for longitudinal monitoring.
• The treatment induced pyroptosis, ferroptosis, and RNA interference, leading to sustained tumor suppression.

Conclusions:

• This study introduces the first photoactivatable, RNA-targeted MR/FL imaging probe for HCC.
• The developed strategy integrates MRI signal amplification, long-term tumor retention, and multi-pathway therapy for comprehensive HCC management.
• This approach establishes a new paradigm for synergistic cancer imaging and treatment.