Fresh off the press! On behalf of Theralase.
Interestingly:
- 4.4. Effect of transferrin as a transporter
Ru(II) containing photosensitizers for photodynamic therapy: A critique on reporting and an attempt to compare efficacy Volume 470, 1
November 2022, 214712
ManjunathaAnkathatti MunegowdaaAngelicaManalacabMadrigalWeersinkaSherri A.McFarlandcLotharLilgeab - a
- Princess Margaret Cancer Centre, University Health Network, Toronto, Ontario, Canada
- b
- Dept Medical Biophysics, University of Toronto, Toronto, Ontario, Canada
- c
- Dept of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, USA
Received 21 December 2021,
Accepted 3 July 2022,
Available online 26 July 2022,
Version of Record 26 July 2022.
Keywords
Photodynamic therapy, Photodynamic threshold,
TLD1433, Photosensitizer
Highlights
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A novel approach to assess the in vitro efficacy of Ru(II) photosensitizers.
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The approach is independent of the PDT activation wavelength.
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The efficacy values are spread over 7 orders of magnitude.
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Abstract
Ruthenium(II)-based coordination complexes have emerged as photosensitizers (PSs) for photodynamic therapy (PDT) in oncology as well as antimicrobial indications and have great potential. Their modular architectures that integrate multiple ligands can be exploited to tune cellular uptake and subcellular targeting, solubility, light absorption, and other photophysical properties. A wide range of Ru(II) containing compounds, as well as other coordination complexes, have been reported as PSs for PDT or as photochemotherapy (PCT) agents. Many studies employ a common scaffold that is subject to systematic variation in one or two ligands to elucidate the impact of these modifications on the photophysical and photobiological performance. Studies that probe the excited state energies and dynamics within these molecules are of fundamental interest and are used to design next-generation systems. However, a comparison of the PDT efficacy between Ru(II) containing PSs and 1st or 2nd generation PSs, already in clinical use or in preclinical/clinical studies, is rare. Even comparisons between Ru(II)-containing molecular structures are difficult, given the wide range of excitation wavelengths, power densities, and cell lines utilized. Despite this gap, PDT dose metrics to quantify PS efficacy are available to perform qualitative comparisons. Such models are independent of excitation wavelength and are based on common outcome metrics, such as the photon density absorbed by the Ru(II) compound to cause 50% cell kill (LD50) based on the previously established threshold model.
In this focused photophysical review, we identified all published studies on Ru(II)-containing PSs since 2005 that reported the required photophysical, light treatment, and in vitro outcome data to permit the application of the Photodynamic Threshold Model to quantify their potential efficacy. The resulting LD50 values range from less than 1013 to above 1020 [hν cm−3], indicating a wide range in PDT efficacy and required optical energy density for ultimate clinical translation.