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Molecularly Engineered Dual-Lock Activatable NIR-II Fluorogenic Probe for Precision Tumor Resection and Real-Time

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  • 1NHC Key Laboratory of Tropical Disease Control, Engineering Research Center for Hainan Bio-Smart Materials and Bio-Medical Devices, Key Laboratory of Hainan Functional Materials and Molecular Imaging, School of Life Sciences and Medical Technology, Hainan Medical University, Haikou, Hainan 571199, China.

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We developed novel fluorescent probes for real-time cancer surgery. These probes precisely visualize tumor margins and monitor treatment effectiveness, improving precision oncology outcomes.

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Area of Science:

  • Oncology
  • Biomedical Engineering
  • Molecular Imaging

Background:

  • Complete surgical resection is crucial for solid tumor treatment.
  • Intraoperative tumor margin visualization and real-time response monitoring remain clinical challenges.

Purpose of the Study:

  • To engineer novel dual-activatable near-infrared-II (NIR-II) fluorescent probes.
  • To enable simultaneous detection of tumor malignancy and therapeutic response.

Main Methods:

  • Designed and synthesized a series of tandem-locked, dual-activatable NIR-II fluorescent probes (HY-1-NO2 to HY-4-NO2).
  • Evaluated probe performance based on response to nitroreductase (NTR) and microenvironmental viscosity.
  • Assessed probe efficacy in delineating tumor margins and monitoring therapeutic response in preclinical models and clinical specimens.

Main Results:

  • HY-2-NO2 exhibited a 20-fold fluorescence enhancement in the NIR-II window (910 nm) upon dual activation.
  • Achieved precise intraoperative tumor margin delineation with accuracy down to 0.2 mm.
  • Demonstrated real-time monitoring of paclitaxel treatment efficacy, with fluorescence intensity correlating positively with tumor suppression.
  • Successfully differentiated tumor from normal tissues in clinical specimens.

Conclusions:

  • Developed an integrated theranostic platform for real-time surgical navigation and functional treatment monitoring.
  • The dual-activatable probe addresses critical needs in precision oncology.
  • Demonstrated strong translational potential for improved cancer care.