Basic Info of the Study
Research by: University of Texas at Arlington, US. One of the leading groups in photoactive drug discovery. Developed first clinical-level rubidium-based PS (TLD-1433), now in Theralase-sponsored Phase 2 trials for bladder cancer.
Modulight products: ML8500 (445 nm, 525 nm, 630 nm, 753 nm, 810 nm)
Laser use: Photoactive drug discovery
Research topics: Medicinal inorganic chemistry and drug discovery. Special interest in synthesis of novel transition metal complexes and studying their interactions with light for the purpose of exploiting those interactions for PDT and photochemotherapy. Rational manipulation of photophysics of the molecules to produce very potent photosensitizing effects, especially in hypoxic conditions and with varying wavelengths.
Other collaborations with Acadia University, UNC at Greensboro, Wake Forest Cancer Center & Roswell Park.
Study protocol to determine wavelength, fluence, and irradiance activities of Os-4T:
- Lead in compound family (Os-4T) was applied to SK-MEL-28 melanoma cells in well-plates
- Well-by-well illuminations with the ML8500 (37 ⁰C, 5% CO2) in triplicate (± SD) using 10–300 J cm−2 fluence and either 525 nm or 630 nm wavelength.
- Determine cell viability with Resazurin assay and read absorbance at 570 and 600 nm. Resazurin assay principle: The irreversible reaction of purple resazurin to pink-colored resorufin is proportional to aerobic respiration, indicating the amount of viable cells.
Graphs from the original publication. Reproduced with permission from the contact author of the publication.
Illumination parameters significantly affected the phototoxicity of Os-4T. Green light was more effective than red light at lower fluences, while maximal potency was achieved at 100 J/cm2 with both wavelengths. The irradiance dependence results show that the phototoxicity with red light can be improved at defined fluence by lowering the irradiance or increasing the concentration of Os-4T. This flexibility with parameters is advantageous when progressing to in vivo models.
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Breaking the barrier: an osmium photosensitizer with unprecedented hypoxic phototoxicity for real world photodynamic therapy
John A. Roque, III, Patrick C. Barrett, Houston D. Cole, Liubov M. Lifshits, Ge Shi, Susan Monro, David von Dohlen, Susy Kim, Nino Russo, Gagan Deep,d Colin G. Cameron, Marta E. Alberto and Sherri A. McFarland
Chemical Science, 2020, 36
Near-infrared absorbing Ru(ii) complexes act as immunoprotective photodynamic therapy (PDT) agents against aggressive melanoma
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