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Updated: Jan 10, 2026
A Bright NIR-II Fluorescence Probe for Vascular and Tumor Imaging
Published on: March 17, 2023
Molecularly Engineered Dual-Lock Activatable NIR-II Fluorogenic Probe for Precision Tumor Resection and Real-Time
Jiao Lu1,2, Xinyu Song3, Xunkai Wang1,2
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.
Abstract:
Despite advancements in multimodal cancer therapies, complete surgical resection remains the cornerstone of curative treatment for solid tumors. However, the inability to precisely visualize tumor margins intraoperatively and monitor therapeutic responses in real-time poses significant clinical challenges. Through rational molecular engineering strategy, we propose a novel class of tandem-locked, dual-activatable NIR-II fluorescent probes (HY-1-NO2 to HY-4-NO2) engineered for simultaneous response to NTR and microenvironmental viscosity, two biomarkers strongly associated with tumor malignancy and treatment response. Among all of the designed probes, HY-2-NO2 demonstrates robust NIR-II emission at 910 nm with a 20-fold enhancement in fluorescence upon activation. This dual-key mechanism ensures high specificity and minimal background, enabling accurate intraoperative delineation of tumor margins with precision down to 0.2 mm. Furthermore, HY-2-NO2 facilitates real-time evaluation of the paclitaxel-induced therapeutic response, with fluorescence intensity positively correlating with tumor suppression. The probe also successfully distinguishes tumor from normal tissues in clinical specimens, demonstrating strong translational potential. Thus, this study provides an integrated theranostic platform that combines real-time surgical navigation with functional monitoring of treatment efficacy, addressing critical gaps in precision oncology.
Insights
We developed novel fluorescent probes for real-time cancer surgery. These probes precisely visualize tumor margins and monitor treatment effectiveness, improving precision oncology outcomes.
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.
