Ruthenium-Based Sonoafterglow Probes for Tumor-Specific Theranostics

Area of Science:

• Biomedical Engineering
• Materials Science
• Chemical Biology

Background:

• Afterglow imaging offers improved signal-to-background ratios for in vivo diagnostics by suppressing autofluorescence.
• Conventional photoactivated afterglow methods are limited by the need for external light sources.
• Developing novel sonoafterglow probes is crucial for advancing ultrasound-triggered imaging and therapy.

Purpose of the Study:

• To design and synthesize novel hybrid molecular sonoafterglow luminophores for enhanced in vivo diagnostics and therapy.
• To investigate the structure-activity relationship of linker types (conjugated alkyne vs. nonconjugated amide) on sonoafterglow emission.
• To develop an activatable sonoafterglow probe for targeted cancer imaging and sonodynamic therapy.

Main Methods:

• Synthesis of two hybrid molecular sonoafterglow luminophores, cRuPA and ncRuPA, incorporating a ruthenium(II) complex and an afterglow substrate with different linkers.
• Evaluation of sonoafterglow properties of cRuPA and ncRuPA upon ultrasound treatment.
• Development of ncRuPA into an activatable probe (ncRuPA_APN) targeting cancer biomarker aminopeptidase N.
• Assessment of ncRuPA_APN for tumor imaging and sonodynamic therapy in vivo.

Main Results:

• ncRuPA, featuring a nonconjugated amide linker, demonstrated strong sonoafterglow emission, unlike cRuPA with a conjugated alkyne linker.
• The nonconjugated amide in ncRuPA stabilized the dioxetane intermediate, enabling sustained luminescence after ultrasound activation.
• The activatable probe ncRuPA_APN showed selective sonoafterglow activation in response to aminopeptidase N.
• ncRuPA_APN facilitated sensitive tumor imaging and effective sonodynamic therapy through ultrasound-triggered singlet oxygen production.

Conclusions:

• The developed Ru-based sonoafterglow probes are the first of their kind, offering a new platform for molecular design.
• Sonoafterglow imaging and therapy offer a promising alternative to light-activated methods for cancer theranostics.
• These findings open new avenues for developing advanced molecular tools for theranostic applications.