In vitro illumination using ML8500: osmium-based anticancer photosensitizer with highest hypoxic activity reported to date

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

Link to the study:

Dr. Sherri McFarland (see her referral of Modulight)

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:

The following steps are extraction of the illumination study from the original research.

 

  1. Lead in compound family (Os-4T) was applied to SK-MEL-28 melanoma cells in well-plates

  1. Well-by-well illuminations in triplicates with the ML8500 (37 ⁰C, 5% CO2) using 525 nm and 630 nm wavelengths. In first experiment irradiance was kept constant at 300 mW/cm2 and fluence was varied between 10-300 J/cm2, while in second experiment fluence was constant at 100 J/cm2 and irradiance varied 25-300 mW/cm2.

  1. 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.

Key observations

Illumination parameters significantly affected the phototoxicity of Os-4T. Green light (525 nm) was more effective than red light (630 nm) at lower fluences, while maximal potency was achieved at both wavelengths when using fluences higher than 100 J/cm2. Irradiance affected the potency with both red and green light that were more effective when lower irradiances were used.

 


Graphs from the original publication. Open-access content reproduced with permission from the contact author of the publication.

 

 

Conclusions:
Light dosimetry experiments showed that the phototoxicity of Os-4T can be improved either by increasing the fluence or lowering the irradiance. Os-4T could be activated with both green and red light but green light was more effective. This flexibility with light parameters is beneficial when progressing to in vivo models.

 

Related Modulight products and Services

ML8500 – Automated Illumination for Microplates »   

 

Related Publications

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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