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Recent advances in functional activatable probes for oncological surgery: Illuminating precision or hindering
Jialiang Lu1, Weihao Zhuang1, Xiaowu Dong2
1Zhejiang Cancer Hospital, Hangzhou, Zhejiang, 310022, China.
Abstract:
Fluorescence-guided surgery has advanced significantly by developing activatable probes that selectively illuminate tumors by responding to microenvironmental biomarkers, minimizing background noise, and improving tumor-to-normal ratios. Unlike conventional "Always-on" probes, activatable designs leverage tumor-specific triggers-such as enzymatic activity, acidic pH, hypoxia, or redox imbalances-to achieve precise fluorescence unmasking. Recent innovations include single-stimuli probes with rapid activation kinetics for real-time intraoperative imaging and multi-stimuli systems to enhance specificity. Targeted strategies for integrating ligands for folate receptors, integrins, or PSMA further improve tumor accumulation. Despite preclinical success, clinical translation remains limited. The field now prioritizes interdisciplinary collaboration to address probe stability, safety, and reproducibility challenges, aiming to bridge the gap between molecular innovation and surgical practicality. By harmonizing probe design with clinical needs, activatable fluorescence imaging promises to redefine precision in oncological surgery, though scalability demands concerted efforts in probe rational design and technology integration.
Insights
Activatable fluorescent probes enhance tumor visualization in surgery by responding to specific biomarkers. This precision imaging approach aims to improve oncological surgery outcomes, though clinical translation requires further development.
Area of Science:
- Biomedical Engineering
- Surgical Oncology
- Molecular Imaging
Background:
- Conventional "Always-on" fluorescent probes lack specificity.
- Activatable probes offer improved tumor-to-normal ratios by responding to tumor microenvironment.
- Tumor-specific triggers include enzymatic activity, pH, hypoxia, and redox imbalances.
Purpose of the Study:
- To review advancements in activatable fluorescent probes for oncological surgery.
- To highlight strategies for enhancing probe specificity and tumor accumulation.
- To discuss challenges and future directions for clinical translation.
Main Methods:
- Development of single- and multi-stimuli activatable probes.
- Integration of targeting ligands (e.g., folate receptors, integrins, PSMA).
- Preclinical evaluation of probe performance in tumor models.
Main Results:
- Activatable probes demonstrate selective fluorescence unmasking in response to tumor biomarkers.
- Targeted strategies improve probe accumulation in tumors.
- Innovations include rapid activation kinetics and enhanced specificity.
Conclusions:
- Activatable fluorescence imaging holds promise for redefining precision in oncological surgery.
- Interdisciplinary collaboration is crucial to address challenges in probe stability, safety, and reproducibility.
- Scalability and integration into surgical practice require further research and development.
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