TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro

Our plain-English summary of TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro, by S. Chamberlain, H.D. Cole, J. Roque, et al (Pharmaceuticals, 2020).

The study

• Authors: S. Chamberlain, H.D. Cole, J. Roque, D. Bellnier, S.A. McFarland, G. Shafirstein
• Journal: Pharmaceuticals
• Published: 2020;13(7)
• Cited by: 28 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Intra-operative photodynamic therapy (IO-PDT) in combination with surgery for the treatment of non-small cell lung cancer and malignant pleural mesothelioma has shown promise in improving overall survival in patients. Here, we developed a PDT platform consisting of a ruthenium-based photosensitizer (TLD1433) activated by an optical surface applicator (OSA) for the management of residual disease. Human lung adenocarcinoma (A549) cell viability was assessed after treatment with TLD1433-mediated PDT illuminated with either 532- or 630-nm light with a micro-lens laser fiber. This TLD1433-mediated PDT induced an EC50 of 1.98 μM (J/cm2) and 4807 μM (J/cm2) for green and red light, respectively. Cells were then treated with 10 µM TLD1433 in a 96-well plate with the OSA using two 2-cm radial diffusers, each transmitted 532 nm light at 50 mW/cm for 278 s. Monte Carlo simulations of the surface light propagation from the OSA computed light fluence (J/cm2) and irradiance (mW/cm2) distribution. In regions where 100% loss in cell viability was measured, the simulations suggest that >20 J/cm2 of 532 nm was delivered. Our studies indicate that TLD1433-mediated PDT with the OSA and light simulations have the potential to become a platform for treatment planning for IO-PDT.

In plain English

This laboratory study used cells grown in plates; it involved no people, no asbestos and no mesothelioma cells. The authors tested a light-activated drug, TLD1433, on human lung adenocarcinoma cells (A549), with eventual use in chest surgery for pleural malignancy in mind. Without light, the drug did not harm the cells at up to 60 µM. With green (532 nm) light (28 mW/cm2, 20 J/cm2), the concentration halving viability was 0.099 plus or minus 0.001 µM. Red (630 nm) light, at a higher dose (65 mW/cm2, 230 J/cm2), gave 20.9 plus or minus 3.5 µM, so green was more potent, though adjusted settings gave similar killing. Green light was then delivered through a flexible optical surface applicator to cells given 10 µM of the drug. Simulations suggested 5 J/cm2 halved viability and 20 J/cm2 meant 100% loss. Tissue-like layers 3 and 5 mm thick weakened the effect, but it persisted through 3 mm. The authors concluded the approach can be used to treat these cells; animal studies are underway. One author invented two issued patents on the drug; two others co-invented a patent application, owned by Roswell Park, for the device.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: In vitro laboratory experiment on a cancer cell line, combined with Monte Carlo computer simulations of light delivery
• Who was studied: Human lung adenocarcinoma cells (A549 line) bought from ATCC, plated at 2500 cells per well, with experiments done in triplicate. There were no human or animal subjects and no mesothelioma cells.
• Exposure: No asbestos exposure was studied. Cells were treated with the ruthenium-based photosensitizer TLD1433 (0.01 to 60 µM), then exposed to 532-nm (green) or 630-nm (red) laser light. The light came either from a laser fiber with a micro-lens or through an optical surface applicator, with or without tissue-mimicking phantoms 3 or 5 mm thick.
• Main results:
  • Without light, TLD1433 was not toxic to A549 cells over the concentrations tested. The concentration needed to halve viability was much greater than the highest concentration tested, 60 µM.
  • With 532-nm light at 28 mW/cm2 and 20 J/cm2, the EC50 in A549 cells was 0.099 plus or minus 0.001 µM, giving a phototherapeutic index of much greater than 600.
  • With 630-nm light at 65 mW/cm2 and 230 J/cm2, the EC50 was 20.9 plus or minus 3.5 µM. Photocytotoxicity was attenuated more than 200-fold compared with green light.
  • The EC50 dose products were 1.98 µM (J/cm2) for green light and 4807 µM (J/cm2) for red light, a 2400-fold difference.
  • Similar photocytotoxicity could be obtained at the two wavelengths by changing the TLD1433 concentration, the fluence and the irradiance.
  • With the optical surface applicator, the 3- and 5-mm phantoms reduced the light and left more cells viable than with no phantom. Treatment was still effective through the 3-mm phantom.
  • In cells treated with 10 µM TLD1433, the simulations suggested that 5 J/cm2 produced the EC50 and that 20 J/cm2 corresponded to a 100% loss of cell viability.
  • On the edge of the plate that was not in direct contact with the applicator, cell viability remained above 60%.
• The authors' conclusion: The authors concluded that TLD1433-mediated PDT with the optical surface applicator can be used to treat A549 cells and that 532-nm light is more potent than 630-nm light. They also concluded that the simulation software is a promising platform for pretreatment planning, and said animal studies are underway.
• Limitations the authors state:
  • The proposed explanation for green light's greater potency (more reactive oxygen production) is not yet confirmed.
  • More in vivo work is needed to assess this speculation.
  • The 96-well plate was not included in the light simulation.

Topics

Medical terms in this study, explained in our Lexicon: Lung Cancer, Non-Small Cell Lung Cancer, Pleural Mesothelioma, Overall Survival, Lung Adenocarcinoma.

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