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

Siyu Lu1, Jing Wu1,2, Shuxin Lyu3

  • 1Department of Radiology, School of Pharmaceutical Sciences, Zhongnan Hospital of Wuhan University, Wuhan University, Wuhan 430071, China.

Analytical Chemistry
|November 13, 2025
PubMed
Summary

Researchers developed tH7@CT8, a dual-modal contrast agent for enhanced cancer diagnostics. This organic nanoprobe improves photoacoustic imaging and near-infrared II fluorescence imaging for better tumor detection and guidance.

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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.