Ir-organometallic compounds-mediated internal and external dual-phototheranostics for collaborative antitumor...

Area of Science:

• Biomedical Engineering
• Materials Science
• Oncology

Background:

• Cerenkov light excitation offers potential for deeper tissue penetration in optical imaging and therapy compared to external light sources.
• Current limitations in Cerenkov light intensity and wavelength restrict its application in tumor theranostics.
• Organometallic compounds offer versatile platforms for developing advanced theranostic agents.

Purpose of the Study:

• To develop a novel radio-phototheranostic agent by integrating organometallic compounds with radionuclide activation.
• To achieve radionuclide-activated near-infrared (NIR) photosensitization exceeding 800 nm for enhanced tumor imaging and therapy.
• To design a dual-function agent for both internal (Cerenkov) and external light-activated phototherapy with synergistic effects.

Main Methods:

• Synthesis of dual-function iridium-organometallic compounds (IR-C6Ir) by linking coumarin 6 and IR775 derivatives via iridium.
• Evaluation of IR-C6Ir accumulation in tumor mitochondria.
• Assessment of anti-tumor efficacy using a combination of Fluorine-18 (18F) radionuclide and 808 nm laser irradiation.
• Investigation of synergistic effects between internal and external phototherapy modalities.

Main Results:

• IR-C6Ir compounds demonstrated preferential accumulation in tumor mitochondria.
• Significant tumor inhibition was achieved, with a 92.5% tumor volume reduction at low concentrations (0.65 µM) and excitation levels (0.5 W/cm² laser, 800 µCi 18F).
• The dual phototherapy approach exhibited a synergistic "1+1>2" enhancement effect.
• Tumor multiplex visualization was successfully achieved using the developed agent.

Conclusions:

• The developed IR-C6Ir represents the first radionuclide-activated NIR photosensitizer operating beyond 800 nm.
• The innovative "internal-external attack" and "two-in-one" energy transfer design enables high-efficiency, low-toxicity phototherapy.
• This strategy offers a promising new avenue for advanced tumor theranostics and multiplex imaging.