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In Vitro and In Vivo Evaluation of Photocontrolled Biologically Active Compounds - Potential Drug Candidates for Cancer Photopharmacology
Published on: September 29, 2023
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A Lock-and-Kill Anticancer Photoactivated Chemotherapy Agent†
Erik Pieter van Geest1, Sina Katharina Götzfried1, David M Klein1
1Leiden Institute of Chemistry, Leiden University, Leiden, The Netherlands.
Photochemistry and Photobiology
|October 31, 2022
Summary
Researchers developed a traceable ruthenium prodrug for photoactivated chemotherapy (PACT). Upon cellular uptake and hydrolysis, the prodrug releases a cytotoxic drug and generates singlet oxygen, demonstrating a light-activated cancer treatment strategy.
Area of Science:
- Coordination Chemistry
- Photodynamic Therapy
- Cancer Prodrug Development
Background:
- Ruthenium complexes are promising for photoactivated chemotherapy (PACT).
- Tracking ruthenium prodrug localization in tumors remains a challenge.
- Existing PACT strategies require precise control over light activation.
Purpose of the Study:
- To develop a traceable ruthenium-based prodrug for PACT.
- To demonstrate intracellular activation and targeted drug release.
- To validate the 'lock-and-kill' principle for cancer treatment.
Main Methods:
- Synthesis of a novel ruthenium PACT prodrug, [Ru(3)(biq)(STF-31)](PF6)2, incorporating a pyrene fluorophore.
- Evaluation of fluorescence quenching and recovery upon ester hydrolysis for cellular uptake tracking.
- Assessment of dark and light cytotoxicity of liposome-encapsulated prodrug in A375 melanoma cells.
Main Results:
- The synthesized ruthenium prodrug exhibited fluorescence quenching, which was recovered upon intracellular hydrolysis, indicating successful uptake.
- Light irradiation of the prodrug released the cytotoxic STF-31 and generated singlet oxygen.
- Liposome-embedded prodrug showed enhanced cytotoxicity upon light activation in melanoma cells.
Conclusions:
- The study presents a functional ruthenium PACT prodrug with built-in tracking capabilities.
- The 'lock-and-kill' mechanism was successfully demonstrated in vitro.
- This approach offers potential for developing targeted cancer therapies with controlled light activation.
