Trimerization-Enhanced NIR-II/Photoacoustic Nanoprobes for Precision Osteosarcoma Imaging.

Area of Science:

• Biomedical Engineering
• Nanotechnology
• Medical Imaging

Background:

• Dual-modal imaging agents are crucial for cancer diagnostics.
• Developing high-performance agents integrating photoacoustic imaging (PAI) and near-infrared II (NIR-II) fluorescence imaging presents challenges.
• Existing small-molecule agents often have limitations in photothermal conversion efficiency (PTCE).

Purpose of the Study:

• To engineer a novel organic nanoprobe, tH7@CT8, for dual-modal PAI and NIR-II fluorescence imaging.
• To address the limitations of small-molecule agents by enhancing PTCE through fluorophore trimerization.
• To improve tumor targeting and imaging performance in osteosarcoma models.

Main Methods:

• Fluorophore trimerization of H7 ([1,2,5]thiadiazolo[3,4-g]quinoxaline derivative) to create tH7.
• Encapsulation of tH7 within an osteosarcoma-targeting amphiphilic matrix to form nanoparticles (tH7@CT8).
• Evaluation of nanoparticle characteristics, including size, fluorescence quantum yield, PTCE, tumor uptake, and in vivo imaging performance in orthotopic osteosarcoma models.

Main Results:

• Trimerization of H7 suppressed fluorescence quantum yield but significantly amplified PTCE to 43.1%.
• The resulting nanoparticles (72 ± 19 nm) showed 4-fold enhanced tumor uptake compared to nontargeted controls.
• In vivo studies demonstrated effective PAI detection and real-time NIR-II guidance with tumor-to-background ratios >12:1.

Conclusions:

• The study presents a successful molecular design strategy for dual-modal organic contrast agents.
• Fluorophore trimerization is an effective method to enhance PTCE while managing fluorescence properties.
• tH7@CT8 shows significant potential for advancing oncology diagnostics and clinical translation of organic contrast agents.