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Updated: Dec 24, 2025
Facile Preparation and Photoactivation of Prodrug-Dye Nanoassemblies
Published on: February 17, 2023
A two-photon-activated prodrug for therapy and drug release monitoring
Peilian Liu1, Bowen Li, Chenyue Zhan
1State Key Lab of Luminescent Materials & Devices, College of Materials Science & Engineering, South China University of Technology, Guangzhou 510640, P. R. China. shzhwu@scut.edu.cn mcfzeng@scut.edu.cn.
Abstract:
A light-activated cleavage strategy for the concomitant release of active drugs and generation of fluorescence changes is highly desirable. Herein a molecular prodrug featuring real-time monitoring of drug localization and release by manipulating fluorophores has been created by constructing a cleavable structure which comprises a photoremovable coumarinyl, an anticancer drug camptothecin, a cleavable linker and a near infrared fluorescent dye dicyanomethylene-4H-pyran (DCM). The fluorescence of coumarinyl and CPT is completely quenched by the DCM moiety via fluorescence resonance energy transfer (FRET). The internalization of the prodrug by cells and its subsequent intracellular location can be tracked by collecting the red fluorescence of DCM; while the release of active CPT as a result of one- or two-photon irradiation can be monitored by observing the newly emerged fluorescence of CPT under one- or two-photon excitation. The prodrug also shows highly controllable cytotoxicity toward HeLa cells and A549 cells, with low IC50 values of 4.01 and 2.53 μM, respectively, upon light irradiation and with much higher IC50 values (>40 μM) without light irradiation. This strategy may provide an approach for the development of light-activatable theranostic anticancer therapeutics.
Insights
Researchers developed a light-activated prodrug that releases anticancer drugs and generates fluorescence for real-time monitoring. This theranostic approach offers controlled drug delivery and tracking for cancer treatment.
Area of Science:
- Biomedical Engineering
- Organic Chemistry
- Photochemistry
Background:
- Developing light-activated drug delivery systems is crucial for targeted cancer therapy.
- Real-time monitoring of drug localization and release enhances therapeutic efficacy and safety.
Purpose of the Study:
- To create a molecular prodrug for light-triggered release of camptothecin (CPT) and simultaneous fluorescence monitoring.
- To investigate the prodrug's theranostic capabilities, including cellular uptake, drug release kinetics, and light-dependent cytotoxicity.
Main Methods:
- Synthesized a prodrug incorporating a photoremovable coumarinyl group, camptothecin, a cleavable linker, and a near-infrared fluorescent dye (DCM).
- Utilized fluorescence resonance energy transfer (FRET) for fluorescence quenching and subsequent signal generation upon CPT release.
- Evaluated prodrug internalization, intracellular localization via DCM fluorescence, and CPT release under one- or two-photon irradiation.
- Assessed light-dependent cytotoxicity against HeLa and A549 cancer cell lines.
Main Results:
- The prodrug demonstrated efficient fluorescence quenching of coumarinyl and CPT by DCM via FRET.
- Cellular uptake and localization were successfully tracked using DCM's red fluorescence.
- Active CPT release was confirmed by observing CPT's fluorescence upon light irradiation.
- The prodrug exhibited significantly enhanced cytotoxicity upon light activation (low IC50 values) compared to dark conditions (high IC50 values).
Conclusions:
- The developed light-activatable prodrug enables simultaneous drug release and fluorescence-based monitoring of drug localization and release.
- This strategy provides a controllable theranostic approach for anticancer drug delivery.
- The findings suggest potential for developing advanced light-activatable theranostic anticancer therapeutics.
