Photodynamic therapy (PDT) is a two-stage clinical procedure that exposes photosensitizing agents to specific wavelengths of light to either produce reactive oxygen species or aid in drug delivery to selectively destroy cancer cells. While PDT has been shown to provide many benefits compared to traditional chemotherapies, treatment efficacy is limited by the photosensitizing agent’s ability to penetrate the tumor. Transition metal complexes containing ruthenium are promising given their dual ability to produce singlet oxygen species and release drug molecules upon irradiation in tandem with their ability to coordinate to a wide range of ligands. The utilization of 3D cell culture models allows for rapid, high-throughput screening of synthesized ruthenium compounds for cancer treatment. Using mass spectrometry imaging, the depth of drug penetration and the spatial localization of putative byproducts can be determined. Herein, we present the analysis of a 3D cell culture model of colon cancer treated with various ruthenium compounds by mass spectrometry imaging. Matrix assisted laser desorption/ionization (MALDI) mass spectrometry-based techniques were utilized to analyze the penetration depth of the ruthenium complexes over a 24-hour dosing period. After the determination of the minimum time necessary for the ruthenium complex to penetrate to the core of the spheroid, light irradiation experiments were completed to determine metabolites formed after light activation of the PDTs. We will present the ongoing efforts to obtain information from the spatial localizations of the ruthenium treatments and associated metabolites into the efficacy of these complexes as putative PDTs.

Shining a light on cancer therapy: The investigation of ruthenium based photodynamic therapies by mass spectrometry imaging

ACS Spring 2022

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