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pH-Sensitive Ratiometric Fluorescent Probe for Evaluation of Tumor Treatments
Peisen Zhang1,2, Junli Meng3,4, Yingying Li5,6
1Key Laboratory of Colloid, Interface and Chemical Thermodynamics, Institute of Chemistry, Chinese Academy of Sciences, Beijing 100190, China. zhangps@iccas.ac.cn.
Abstract:
Determining therapeutic efficacy is critical for tumor precision theranostics. In order to monitor the efficacy of anti-cancer drugs (e.g., Paclitaxel), a pH-sensitive ratiometric fluorescent imaging probe was constructed. The pH-sensitive ratiometric fluorescent dye ANNA was covalently coupled to the N-terminal of the cell-penetrating TAT peptide through an amidation reaction (TAT-ANNA). The in vitro cellular experiments determined that the TAT-ANNA probe could penetrate the cell membrane and image the intracellular pH in real time. The in vivo experiments were then carried out, and the ratiometric pH response to the state of the tumor was recorded immediately after medication. The TAT-ANNA probe was successfully used to monitor the pharmacodynamics of anti-cancer drugs in vivo.
Insights
A novel pH-sensitive fluorescent probe, TAT-ANNA, was developed to monitor anti-cancer drug efficacy in real-time. This imaging probe successfully tracked tumor responses to therapies like Paclitaxel in vivo.
Area of Science:
- Biomedical Imaging
- Theranostics
- Drug Delivery
Background:
- Accurate monitoring of therapeutic efficacy is crucial for personalized cancer treatment.
- Existing methods for evaluating drug response often lack real-time, in vivo capabilities.
- Tumor microenvironment pH changes can indicate therapeutic effectiveness.
Purpose of the Study:
- To develop a novel pH-sensitive ratiometric fluorescent imaging probe for real-time monitoring of anti-cancer drug efficacy.
- To assess the probe's ability to penetrate cell membranes and image intracellular pH.
- To evaluate the probe's performance in tracking tumor pharmacodynamics in vivo.
Main Methods:
- Constructed a pH-sensitive ratiometric fluorescent probe (TAT-ANNA) by conjugating the dye ANNA to a cell-penetrating peptide (TAT).
- Performed in vitro experiments to confirm cellular uptake and intracellular pH imaging capabilities.
- Conducted in vivo studies to monitor the probe's ratiometric pH response in tumors post-medication.
Main Results:
- The TAT-ANNA probe demonstrated successful cell membrane penetration.
- Real-time intracellular pH imaging was achieved in vitro.
- The probe effectively recorded tumor pH changes in vivo immediately after anti-cancer drug administration, reflecting therapeutic response.
Conclusions:
- The TAT-ANNA probe is a viable tool for real-time, in vivo monitoring of anti-cancer drug pharmacodynamics.
- This imaging approach offers a promising strategy for precision theranostics in oncology.
- The probe's pH sensitivity allows for immediate assessment of tumor response to treatment.
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