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Dual Ratiometric Single-Molecule Theranostic Probes for Photothermal Therapy and Real-Time Quantitative Evaluation of
Shuping Zhang1,2, Xingyue Liu1, Bang-Ping Jiang1
1Key Laboratory for Chemistry and Molecular Engineering of Medicinal Resources (Ministry of Education of China), Guangxi Key Laboratory of Chemistry and Molecular Engineering of Medicinal Resources, School of Chemistry and Pharmaceutical Sciences, Guangxi Normal University, Guilin 541004, P. R. China.
Abstract:
Tracking the quantitative evaluation of therapeutic efficiency in tumors is essential for the precision management of cancer patients. Theranostic probes, which integrate diagnostic molecular imaging and therapeutic capabilities into a single entity, can be used to monitor the treatment process and reflect the therapeutic effect. However, current theranostic probes lack precise quantitative evaluations in vivo due to the use of single-wavelength imaging during tumor therapy. Here we present a portal library of dual ratiometric single-molecule theranostic probes for precise tumor therapy through photothermal therapy (PTT) and quantitative evaluation of tumor cell death in vivo via ratiometric near-infrared fluorescence (NIRF) and ratiometric photoacoustic (PA) imaging. One optimal single-molecule dye is further modified into an activatable probe (AF-1F-NO2), whose dual ratiometric NIRF/PA signal and photothermal activity are only activated in the presence of a tumor biomarker (nitroreductase). By eliciting a dual ratiometric response (NIRF/PA: NIRF850/NIRF750; PA770/PA670) to tumor hypoxia, the new probe acts as a hypoxia-activated PTT theranostic agent, enabling real-time quantitative evaluation in vivo during PTT. Thus, this study not only presents the first dual ratiometric single-molecule theranostic probe for PTT and real-time quantitative evaluation of therapeutic efficacy in vivo, but also opens up a promising paradigm for engineering other single-molecule dual ratiometric theranostic probes in combination with more therapeutic modalities for precision medicine.
Insights
Researchers developed a novel dual ratiometric theranostic probe for precise cancer treatment. This single-molecule agent enables quantitative evaluation of tumor cell death during photothermal therapy (PTT) using advanced imaging techniques.
Area of Science:
- Biomedical Engineering
- Molecular Imaging
- Cancer Therapeutics
Background:
- Precise quantitative evaluation of tumor treatment efficacy is crucial for personalized cancer care.
- Current theranostic probes often lack in vivo quantitative assessment due to single-wavelength imaging limitations.
- Theranostic probes combine diagnostic imaging and therapeutic functions for real-time treatment monitoring.
Purpose of the Study:
- To develop a dual ratiometric single-molecule theranostic probe for precise photothermal therapy (PTT).
- To enable quantitative in vivo evaluation of tumor cell death using ratiometric near-infrared fluorescence (NIRF) and photoacoustic (PA) imaging.
- To create a hypoxia-activated theranostic agent for real-time monitoring during PTT.
Main Methods:
- Designed and synthesized a portal library of dual ratiometric single-molecule theranostic probes.
- Modified an optimal dye into an activatable probe (AF-1F-NO2) responsive to tumor biomarkers like nitroreductase.
- Utilized dual ratiometric NIRF/PA imaging (NIRF850/NIRF750; PA770/PA670) to assess tumor hypoxia and therapeutic response.
- Demonstrated hypoxia-activated PTT and real-time quantitative evaluation in vivo.
Main Results:
- Developed the first dual ratiometric single-molecule theranostic probe for PTT.
- The probe (AF-1F-NO2) showed selective activation in the presence of nitroreductase, indicating tumor-specific targeting.
- Achieved real-time quantitative evaluation of therapeutic efficacy in vivo via dual ratiometric NIRF/PA imaging.
- Demonstrated successful hypoxia-activated PTT with quantitative monitoring of treatment response.
Conclusions:
- The novel dual ratiometric probe enables precise tumor therapy and real-time quantitative evaluation of therapeutic efficacy in vivo.
- This work establishes a promising platform for engineering advanced single-molecule dual ratiometric theranostic probes for precision medicine.
- The developed probe offers a new paradigm for combining therapeutic modalities with quantitative diagnostic imaging.
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