Dataset Information

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

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.

SUBMITTER: Chamberlain S

PROVIDER: S-EPMC7407920 | biostudies-literature | 2020 Jun

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

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

Chamberlain Sarah S Cole Houston D HD Roque John J Bellnier David D McFarland Sherri A SA Shafirstein Gal G

Pharmaceuticals (Basel, Switzerland) 20200628 7

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 PD ...[more]

PMID: 32605213

Similar Datasets

Project description:Introduction: The photosensitizer, meso-tetraphenyl chlorine disulphonate, TPCS2a (Amphinex®) has been evaluated in a proteome analysis of rat bladder cancer cells (AY27) in combination with the chemotherapeutic drug Bleomycin (BML). Photochemical internalization (PCI) is a novel technology for cytosolic delivery of macromolecular therapeutics based on principles of photodynamic therapy (PDT). Since tumor cells have shown to release certain proteins into plasma membrane after PDT1, the we aimed at of this study was to quantifying the amount of endosomal proteins expressed following TPCS2a-PDT or BLM/TPCS2a-based PCI. Methods: AY27 cells were grown in isotopically labeled SILAC medium using the SILAC technology and further incubated with TPCS2a followed by BLM stimulation and blue light illumination (LumiSource, 13mW/cm2). Endosomal proteins were enriched by gradient-ultracentrifugation and measurements of BLM after endosomal uptake were performed by high pressure liquid chromatography (HPLC). Quantitative measurements of the pProteins were performed quantified by Orbitrap mass spectrometry (LC-MS/MS). These rRaw data files were analyzed using Max Quant v 1.5.5.12 thereby, mapping the spectra over rat canonical proteome with isoforms 3. The SILAC ratios hence obtained were log transformed and subjected to Student’s t-test in order to find identify differentially expressed proteins (DEPs) using Perseus platform4. Further these DEPs were mapped to Gene Ontology database to characterize the enrichment of ontological categories. Results: Both upregulated and downregulated DEPs were recorded from total cell extracts as well as from enriched endosomes after gradient-ultracentrifugation and further grouped according to their biological functions. Conclusions: The present work shows that SILAC analysis for in vitro PDT and PCI treatment is a promising technology approach for characterizing different processes related to e.g. cell death during PDT/PCI5 treatment based on quantified DEPs in these different conditions, respectively.

Project description:Photodynamic therapy (PDT) is an effective antimicrobial therapy that we used to treat human abscess cavities in a Phase 1 clinical trial. This trial included pre-PDT measurements of abscess optical properties, which affect light dose (light fluence) at the abscess wall and PDT response. This study simulated PDT treatment planning for 13 subjects that received optical spectroscopy prior to clinical PDT, to determine the impact of measured optical properties on ability to achieve fluence rate targets in 95% of the abscess wall. Retrospective treatment plans were evaluated for 3 conditions: (1) clinically delivered laser power and assumed, homogeneous optical properties, (2) clinically delivered laser power and measured, homogeneous optical properties, and (3) with patient-specific treatment planning using measured, homogeneous optical properties. Treatment plans modified delivered laser power, intra-cavity Intralipid (scatterer) concentration, and laser fiber type. Using flat-cleaved laser fibers, the proportion of subjects achieving 95% abscess wall coverage decreased significantly relative to assumed optical properties when using measured values for 4 mW cm-2(92% versus 38%,p= 0.01) and 20 mW cm-2(62% versus 15%,p= 0.04) thresholds. When measured optical properties were incorporated into treatment planning, the 4 mW cm-2target was achieved for all cases. After treatment planning, optimal Intralipid concentration across subjects was 0.14 ± 0.09%, whereas 1% was used clinically. Required laser power to achieve the 4 mW cm-2target was significantly correlated with measured abscess wall absorption (ρ= 0.7,p= 0.008), but not abscess surface area (ρ= 0.2,p= 0.53). When using spherical diffuser fibers for illumination, both optimal Intralipid concentration (p= 0.0005) and required laser power (p= 0.0002) decreased compared to flat cleaved fibers. At 0% Intralipid concentration, the 4 mW cm-2target could only be achieved for 69% of subjects for flat-cleaved fibers, compared to 100% for spherical diffusers. Based on large inter-subject variations in optical properties, individualized treatment planning is essential for abscess photodynamic therapy. (Clinical Trial Registration: The parent clinical trial from which these data were acquired is registered on ClinicalTrials.gov as 'Safety and Feasibility Study of Methylene Blue Photodynamic Therapy to Sterilize Deep Tissue Abscess Cavities,' with ClinicalTrials.gov identifier NCT02240498).

Dataset Information

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

Publications

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

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets