In Situ Synthesis of a Tumor Microenvironment-Activated Radiosensitizing Cu_2-xS/LDH Probe for Photoacoustic...

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Oncology

Background:

• Efficient delivery of theranostic nanoprobes to tumors is challenging for imaging and treatment.
• Current methods often lack specificity and efficacy in tumor microenvironments.

Purpose of the Study:

• To develop a novel strategy for in situ generation of nanoprobes within tumors.
• To enable responsive photoacoustic imaging and targeted radiotherapy for colorectal cancer.

Main Methods:

• Designed an organic-inorganic hybrid nanoprobe (CAL-IR) using copper-based layered double hydroxide (Cu-LDH) and IR-806.
• Investigated in situ transformation into copper sulfide (Cu2-xS) nanoparticles triggered by hydrogen sulfide (H2S).
• Evaluated the enhanced near-infrared absorption and radiosensitization properties of the transformed nanostructure.

Main Results:

• The CAL-IR nanoprobe transformed in situ into Cu2-xS/LDH heterojunctions in tumor microenvironments.
• The transformed nanostructure showed enhanced near-infrared absorption for photoacoustic imaging.
• Demonstrated improved radiotherapy efficacy via H2S consumption, reduced X-ray attenuation, and intrinsic radiosensitization.
• Achieved high-contrast photoacoustic imaging and enhanced radiotherapy outcomes in mouse models with minimal off-target effects.

Conclusions:

• The in situ generated nanoprobes offer a promising approach for precision tumor imaging and enhanced radiotherapy.
• CAL-IR demonstrates significant clinical potential for treating colorectal cancer.
• This responsive nanoprobe system overcomes delivery challenges and improves therapeutic efficacy.