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

2020 ◽  
Vol 13 (7) ◽  
pp. 137 ◽  
Author(s):  
Sarah Chamberlain ◽  
Houston D. Cole ◽  
John Roque ◽  
David Bellnier ◽  
Sherri A. McFarland ◽  
...  

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.

2010 ◽  
Vol 43 (10) ◽  
pp. 1001-1009 ◽  
Author(s):  
A.O. Santos ◽  
J.P. Pereira ◽  
M.C. Pedroso de Lima ◽  
S. Simões ◽  
J.N. Moreira

Lung Cancer ◽  
1990 ◽  
Vol 6 (1-2) ◽  
pp. 63
Author(s):  
W Matthews ◽  
J Cook ◽  
JB Mitchell ◽  
RR Perry ◽  
S Evans ◽  
...  

2020 ◽  
Author(s):  
Deborah A. Smithen ◽  
Susan Monro ◽  
Mitch Pinto ◽  
John A. Roque III ◽  
Roberto M. Diaz-Rodriguez ◽  
...  

A new family of ten dinuclear Ru(II) complexes based on the bis[pyrrolyl Ru(II)] triad scaffold, where two Ru(bpy)<sub>2</sub> centers are separated by a variety of organic linkers, was prepared to evaluate the influence of the organic chromophore on the spectroscopic and in vitro photodynamic therapy (PDT) properties of the compounds. The bis[pyrrolyl Ru(II)] triads absorbed strongly throughout the visible region, with several members having molar extinction coefficients (e) ≥10<sup>4</sup> at 600–620 nm and longer. Phosphorescence quantum yields were generally less than 0.1% and in some cases undetectable. The singlet oxygen quantum yields ranged from 5% to 77% and generally correlated with their photocytotoxicities toward human leukemia (HL-60) cells regardless of the wavelength of light used. Dark cytotoxicities varied ten-fold, with EC<sub>50</sub> values in the range of 10–100 µM and phototherapeutic indices (PIs) as large as 5,400 and 260 with broadband visible (28 J cm<sup>-2</sup>, 7.8 mW cm<sup>-2</sup>) and 625-nm red (100 J cm<sup>-2</sup>, 42 mW cm<sup>-2</sup>) light, respectively. The bis[pyrrolyl Ru(II)] triad with a pyrenyl linker (5h) was especially potent, with an EC50 value of 1 nM and PI >27,000 with visible light and subnanomolar activity with 625-nm light (100 J cm<sup>-2</sup>, 28 mW cm<sup>-2</sup>). The lead compound 5h was also tested in a tumor spheroid assay using the HL60 cell line and exhibited greater photocytotoxcicity in this more resistant model (EC<sub>50</sub>=60 nM and PI>1,200 with 625-nm light) despite a lower dark cytotoxicity. The in vitro PDT effects of 5h extended to bacteria, where submicromolar EC<sub>50</sub> values and PIs >300 against <i>S. mutans</i> and <i>S. aureus </i>were obtained with visible light. This activity was attenuated with 625-nm red light, but PIs were still near 50. The ligand-localized <sup>3</sup>ππ* state contributed by the pyrenyl linker of 5h likely plays a key role in its phototoxic effects toward cancer cells and bacteria.<br><br>


2D Materials ◽  
2021 ◽  
Author(s):  
Giacomo Reina ◽  
Amalia Ruiz ◽  
Barbara Richichi ◽  
Giacomo Biagiotti ◽  
Gina Elena Giacomoazzo ◽  
...  

Abstract Boron dipyrromethene derivates (BODIPYs) are promising photosensitisers (PSs) for cancer treatment using photodynamic therapy (PDT). This study investigates the functionalisation of graphene oxide (GO) with a BODIPY derivate for glutathione (GSH) depletion and PDT. The functionalisation of GO with a 3,5-dichloro-8-(4-boronophenyl) BODIPY via a diol derivatisation with the phenyl boronic acid moiety at the meso position of the BODIPY core, allowed to preserve the intrinsic properties of GO. We demonstrated that both chlorine atoms were substituted by GSH in the presence of glutathione transferase (GST), inducing a relevant bathochromic shift in the absorption/emission features and thus generating the active PS. Ex vitro assessment using cell lysates containing cytoplasmatic GST revealed the intracellular catalytic mechanism for the nucleophilic substitution of the GO-BODIPY adduct with GSH. Confocal microscopy studies showed important differences in the cellular uptake of free BODIPY and GO-BODIPY and revealed the coexistence of GO-BODIPY, GO-BODIPY-GS, and GO-BODIPY-GS2 species inside vesicles and in the cytoplasm of the cells after 24 h of incubation. In vitro biocompatibility and safety of GO and GO-BODIPY were evaluated in 2D and 3D models of prostate adenocarcinoma cells (PC-3), where no toxicity was observed up to 100 µg/mL of GO/GO-BODIPY in all treated groups 24 h post-treatment (cell viability > 90%). Only a slight decrease to 80% at 100 µg/mL was observed after 48 h of incubation. We demonstrated the efficacy of a GO adduct containing an α-chlorine-substituted BODIPY for the simultaneous depletion of intracellular GSH and the photogeneration of reactive oxygen species using a halogen white light source (5.4 mW/cm2) with a maximum in the range of 500-800 nm, which significantly reduced cell viability (< 50%) after irradiation. Our study provides a new vision on how to apply BODIPY derivates and potentiate the toxicity of PDT in prostate and other types of cancer.


2019 ◽  
Vol 25 (1) ◽  
pp. 1-6 ◽  
Author(s):  
J. A. Rodrigues ◽  
R. Amorim ◽  
M. F. Silva ◽  
F. Baltazar ◽  
R. F. Wolffenbuttel ◽  
...  

1989 ◽  
Vol 47 (3) ◽  
pp. 276-281 ◽  
Author(s):  
Wilbert Matthews ◽  
Walter Rizzoni ◽  
James Mitchell ◽  
Angelo Russo ◽  
Harvey Pass

2015 ◽  
Vol 08 (04) ◽  
pp. 1550017 ◽  
Author(s):  
Xuewei Jiang ◽  
Zhichao Fan ◽  
Yili Yu ◽  
Chenying Shao ◽  
Yuanzhen Suo ◽  
...  

Photodynamic therapy (PDT) has been commonly used in treating many diseases, such as cancer and infectious diseases. We investigated the different effects of PDT on three main pathogenic bacteria of periodontitis — Prevotella melaninogenica (P.m.), Porphyromonas gingivalis (P.g.) and Aggregatibacter actinomycetemcomitans (A.a.). The portable red light-emitting diode (LED) phototherapy device was used to assess the exogenous PDT effects with different light doses and photosensitizer concentrations (Toluidine blue O, TBO). The portable blue LED phototherapy device was used to assess the endogenous PDT effects with the use of endogenous photosensitizers (porphyrin) under different light doses. We found out that both exogenous and endogenous PDT were able to restrict the growth of all the three bacteria significantly. Moreover, the optimal PDT conditions for these bacteria were obtained through this in vitro screening and could guide the clinical PDT on periodontitis.


2021 ◽  
pp. jim-2020-001736
Author(s):  
Yong-Fei Gu ◽  
Xing-Ping Ge

Ubiquitin protein ligase E3 component n-recognin 5 (UBR5) has been identified as an oncogene in diverse cancers; however, whether its expression was associated with radiosensitivities of non-small cell lung cancer (NSCLC) cells remains unclear. Expression levels of UBR5 in NSCLC tissues and cell lines were examined by immunohistochemical staining and western blotting. Colony formation assay, CCK-8 cell viability assay, flow cytometry, and caspase-3 activity assay were performed to evaluate the radiosensitization of UBR5 knockdown in NSCLC cells, and the underlying mechanism in vitro was also investigated. UBR5 was highly expressed in NSCLC tissues, and its high expression was associated with the poor prognosis in 50 patients with NSCLC. After X-ray irradiation, the protein expression levels of UBR5 were also increased in NSCLC cells. UBR5 inhibition enhanced the radiosensitivity of NSCLC cells by inhibiting the cell viability and inducing apoptosis. Further investigation indicated that UBR5 knockdown-mediated radiosensitization involved the phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway. Knockdown of UBR5 radiosensitizes NSCLC cells via the inactivation of the PI3K/AKT signal, which provided a novel therapeutic target for NSCLC radiosensitization.


2012 ◽  
Vol 16 (07n08) ◽  
pp. 802-808 ◽  
Author(s):  
J. Wang ◽  
H. Yan Tang ◽  
W. Li Yang ◽  
J. Yao Chen

The sulfonated aluminum phthalocyanines (AlPcSs), popularly used photosensitizers, were linked on the surfaces of gold nanorods (AuNRs) by the electrostatic binding to form AlPcS–AuNRs conjugates, in order to improve the photo-therapy efficiency of cancer cells by combining the photodynamic therapy (PDT) of AlPcSs and the photothermal therapy (PTT) of AuNRs . The AlPcS's fluorescence is two-fold enhanced when they adhered on the surfaces of AuNRs probably due to the surface Plasmon coupling, which would facilitate the AlPcS detection. The fluorescence images show that AuNRs can carry loaded AlPcSs to penetrate into human nasopharyngeal carcinoma cells with a fast speed, achieving the effective intracellular delivery of AlPcSs . The PTT effect of cellular AuNRs alone under the white light irradiation of 50 minutes decreased the cell viability to 77%, and the PDT effect of cellular AlPcS–AuNRs with filtered red light (670–710 nm) irradiation of 50 min lowered the cell viability to 79%. However, with the same white light irradiation of 50 min, the AlPcS–AuNRs destroyed most cells leaving the cell viability to 28%, reflecting a typical synergistic effect on cell killing. These results suggest that the combination of PTT and PDT with AlPcS–AuNRs is a promising strategy for improving the phototherapy of cancers.


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