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TLD1433-Mediated Photodynamic Therapy Lung Cancer Cells

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TLD1433-Mediated Photodynamic Therapy Lung Cancer Cells ( tld1433-mediated-photodynamic-therapy-lung-cancer-cells )

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pharmaceuticals Article TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro Sarah Chamberlain 1 , Houston D. Cole 2, John Roque III 2,3 , David Bellnier 1, Sherri A. McFarland 2,3,*,† and Gal Shafirstein 1,*,† 1 2 3 * Correspondence: sherri.mcfarland@uta.edu (S.A.M.); gal.shafirstein@roswellpark.org (G.S.) † Principal Investigators. Received: 21 May 2020; Accepted: 26 June 2020; Published: 28 June 2020 Department of Cell Stress Biology, Photodynamic Therapy Center, Roswell Park Comprehensive Cancer Center, Buffalo, NY 14203, USA; sarah.chamberlain@roswellpark.org (S.C.); david.bellnier@roswellpark.org (D.B.) Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX 76019-0065, USA; houston.cole@mavs.uta.edu (H.D.C.); john.roque@uta.edu (J.R.III) Department of Chemistry and Biochemistry, The University of North Carolina at Greensboro, Greensboro, NC 27402-6170, USA 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. Keywords: TLD1433; optical surface applicator; intra-operative photodynamic therapy; PDT; light simulation 1. Introduction There is no effective therapy for patients with non-small cell lung cancer (NSCLC) with pleural dissemination or malignant pleural mesothelioma [1–3]. Intraoperative photodynamic therapy (IO-PDT) with surgery has been reported to improve overall survival in the treatment of NSCLC and malignant mesothelioma, when compared to historical data [4–6]. The current IO-PDT regimen involves systemic administration of a photosensitizer (PS) approximately 24–48 h prior to surgery [7]. During surgery, after removal of all macroscopic resectable cancer cells and before closing the surgical wound, a therapeutic laser light is delivered to activate the PS and ablate residual viable cancer cells that could remain in the cavity [8]. The light delivery is accomplished with a handheld light source that the treating physician moves within the thoracic cavity to administer a prescribed threshold light dose (fluence, J/cm2) [1,5,7,8]. 􏰁􏰂􏰃 􏰅􏰆􏰇 􏰈􏰉􏰊􏰋􏰌􏰂􏰍 Pharmaceuticals 2020, 13, 137; doi:10.3390/ph13070137 www.mdpi.com/journal/pharmaceuticals

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