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Pharmaceuticals 2020, 13, 137 2 of 9 The delivered light is measured with isotropic detectors that are secured within close-end catheters sutured in about eight anatomical sites that are at high risk for local recurrence due to retention of microscopic cancer cells within the thoracic cavity. Here, we report on the potential use of a novel ruthenium (Ru)-based PS (TLD1433) in ablating lung cancer cells. TLD1433 is a Ru(II) polypyridyl complex that can be classified as a metal-organic dyad. It contains a metal center that facilitates efficient population of triplet excited states (either directly or indirectly) and an organic α-terthienyl group that affords a triplet intraligand charge transfer (3ILCT) excited state with a prolonged lifetime and high sensitivity to oxygen. The 3ILCT states can be populated (i) indirectly via singlet metal-to-ligand charge transfer (1MLCT) and 1ILCT excited states that are formed following absorption of green light, or (ii) directly with red light. The PDT effects obtained with green light are more potent than those with red light owing to the lower molar extinction coefficients of TLD1433 at the red wavelengths. The attenuated PDT effects at longer wavelengths can be improved by formulating TLD1433 with transferrin (Rutherrin), and this has been demonstrated using bladder cancer cells [9]. The choice of wavelength will depend on the desired tissue penetration depth, with green light being preferred when the penetration depth must be kept minimal (to preserve healthy tissue) and red light when a larger margin of treatment is needed. TLD1433 is currently being evaluated in a phase II clinical trial for treating high-risk non-muscle invasive bladder cancer (NMIBC) with PDT. The treatment uses green light to avoid damaging the underlying urothelial muscle tissue. In this indication, TLD1433 demonstrates high retention in bladder cancer cells when administered through instillation (in the bladder) 1 h prior to light delivery [10–12]. The initial results suggest that this treatment is safe, while inducing effective tumor regression. We suggest that TLD1433-mediated IO-PDT can also be used to treat pleural malignancy. We propose to administer TLD1433 by instillation with sterile saline, in the thoracic cavity. Currently, instillation with sterile saline or intralipid is used to improve optical index matching when administering IO-PDT in the thoracic cavity [7]. We expect that TLD1433 will also exhibit high retention in cancer cells compared to normal lung tissue. In this paper we propose to activate TLD1433 with surface illumination using a recently developed optical surface applicator (OSA) [13]. The OSA was designed specifically for efficient light delivery in IO-PDT in the thoracic cavity. So far, the OSA has not yet been validated with TLD1433. The purpose of the present study was to test whether the OSA could be used to activate TLD1433 for the destruction of lung cancer cells in vitro before moving to in vivo studies. The OSA’s novel construction allows precise adjustments of the light irradiance (mW/cm2) and fluence that are key parameters for effective PDT [14,15]. The OSA includes optical fibers for laser light delivery, and dosimetry fibers for light measurements. A detailed description of the OSA can be found in Chamberlain et al. 2019 [13]. Briefly, the OSA is made of a flexible silicon-based mesh of interconnected spheres 10-mm in diameter with parallel channels that enable placement of optical fibers. The fibers are at fixed distance of 5 mm from the mesh surface. This design is expected to reduce the time of light administration with improved control of light irradiance and fluence [13]. Herein, we also present the first simulation of light irradiance and fluence propagation from the OSA. This paper is the first report that highlights the potential use of TLD1433-mediated PDT with the OSA in the treatment of human adenocarcinoma (A549) cells. We studied the response of A549 cells to TLD1433 with two clinically approved light wavelengths: 630 and 532 nm. The spatial distribution of cell viability was compared to the distribution of the simulated light irradiance and fluence, laying the foundation for a pretreatment planning for TLD1433-mediated IO-PDT with OSA for pleural malignancy.PDF Image | TLD1433-Mediated Photodynamic Therapy Lung Cancer Cells
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