Design of a graphene oxide-BODIPY conjugate for glutathione depletion and photodynamic therapy

2D Materials ◽  
2021 ◽  
Author(s):  
Giacomo Reina ◽  
Amalia Ruiz ◽  
Barbara Richichi ◽  
Giacomo Biagiotti ◽  
Gina Elena Giacomoazzo ◽  
...  
Keyword(s):  
Graphene Oxide ◽  
Photodynamic Therapy ◽  
Cell Viability ◽  
Catalytic Mechanism ◽  
Glutathione Transferase ◽  
Bathochromic Shift ◽  
3D Models ◽  
Glutathione Depletion ◽  
In Vitro Biocompatibility

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.

Silicate-doped nano-hydroxyapatite/graphene oxide composite reinforced fibrous scaffolds for bone tissue engineering

2018 ◽  
Vol 32 (10) ◽  
pp. 1392-1405 ◽  
Author(s):  
Ali Deniz Dalgic ◽  
Ammar Z. Alshemary ◽  
Ayşen Tezcaner ◽  
Dilek Keskin ◽  
Zafer Evis
Keyword(s):  
Tissue Engineering ◽  
Graphene Oxide ◽  
Bone Tissue Engineering ◽  
Protein Adsorption ◽  
Bone Tissue ◽  
Three Dimensional ◽  
Osteosarcoma Cell ◽  
In Vitro Biocompatibility ◽  
Microscopy Techniques

In this study, novel graphene oxide–incorporated silicate-doped nano-hydroxyapatite composites were prepared and their potential use for bone tissue engineering was investigated by developing an electrospun poly(ε-caprolactone) scaffold. Nanocomposite groups were synthesized to have two different ratios of graphene oxide (2 and 4 wt%) to evaluate the effect of graphene oxide incorporation and groups with different silicate-doped nano-hydroxyapatite content was prepared to investigate optimum concentrations of both silicate-doped nano-hydroxyapatite and graphene oxide. Three-dimensional poly(ε-caprolactone) scaffolds were prepared by wet electrospinning and reinforced with silicate-doped nano-hydroxyapatite/graphene oxide nanocomposite groups to improve bone regeneration potency. Microstructural and chemical characteristics of the scaffolds were investigated by X-ray diffraction, Fourier transform infrared spectroscope and scanning electron microscopy techniques. Protein adsorption and desorption on material surfaces were studied using fetal bovine serum. Presence of graphene oxide in the scaffold, dramatically increased the protein adsorption with decreased desorption. In vitro biocompatibility studies were conducted using human osteosarcoma cell line (Saos-2). Electrospun scaffold group that was prepared with effective concentrations of silicate-doped nano-hydroxyapatite and graphene oxide particles (poly(ε-caprolactone) – 10% silicate-doped nano-hydroxyapatite – 4% graphene oxide) showed improved adhesion, spreading, proliferation and alkaline phosphatase activity compared to other scaffold groups.

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 ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Photodynamic Therapy ◽  
Cell Viability ◽  
Light Propagation ◽  
Residual Disease ◽  
Red Light ◽  
Optical Surface ◽  
Light Fluence ◽  
532 Nm

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.

Synthesis, Mechanical Properties, and in Vitro Biocompatibility with Osteoblasts of Calcium Silicate–Reduced Graphene Oxide Composites

2014 ◽  
Vol 6 (6) ◽  
pp. 3947-3962 ◽  
Author(s):  
Mehdi Mehrali ◽  
Ehsan Moghaddam ◽  
Seyed Farid Seyed Shirazi ◽  
Saeid Baradaran ◽  
Mohammad Mehrali ◽  
...  
Keyword(s):  
Mechanical Properties ◽  
Graphene Oxide ◽  
Reduced Graphene Oxide ◽  
Calcium Silicate ◽  
In Vitro Biocompatibility ◽  
Reduced Graphene ◽  
Oxide Composites

scholarly journals Enamel Anti-Demineralization Effect of Orthodontic Adhesive Containing Bioactive Glass and Graphene Oxide: an in-Vitro Study

2018 ◽  
Author(s):  
Seung-Min Lee ◽  
Kyung-Hyeon Yoo ◽  
Seog-Young Yoon ◽  
In-Ryoung Kim ◽  
Bong-Soo Park ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Graphene Oxide ◽  
Cell Viability ◽  
Bioactive Glass ◽  
In Vitro Study ◽  
Biological Properties ◽  
Low Viscosity ◽  
Adhesive Remnant Index ◽  
Base Solution

White spot lesions (WSLs), a side effect of orthodontic treatment, can result in reversible and unaesthetic results. Graphene oxide (GO) with a bioactive glass (BAG) mixture(BAG@GO) was added to Low Viscosity Transbond XT(LV) in a ratio of 1, 3, 5%. The composite&rsquo;s characterization and its physical and biological properties were verified with scanning electron microscopy(SEM) and X-ray diffraction(XRD); its microhardness, shear bond stress (SBS), cell viability, and adhesive remnant index (ARI) were also assessed. Efficiency in reducing WSL was evaluated using antibacterial activity of S. mutans. Anti-demineralization was analyzed using a cycle of the acid-base solution. Adhesives with 3 or 5 wt.% of BAG@GO showed significant increase in microhardness compared with LV. The sample and LV groups showed no significant differences in SBS or ARI. The cell viability test confirmed that none of the sample groups showed higher toxicity compared to the LV group. Antibacterial activity was higher in the 48-hour group than in the 24-hour group; the 48-hour test showed that BAG@GO had a high antibacterial effect, which was more pronounced in 5 wt.% of BAG@GO. Anti-demineralization effect was higher in the BAG@GO-group than in the LV-group; the higher the BAG@GO concentration, the higher the anti-demineralization effect.

scholarly journals Evaluation of cell damage and modulation of cytokines TNF-α, IL-6 and IL-10 in macrophages exposed to PpIX-mediated photodynamic therapy

2020 ◽  
Vol 80 (3) ◽  
pp. 497-505
Author(s):  
R. D. R. Tiveron ◽  
D. A. Costa ◽  
M. D. I. Leite ◽  
C. B. S. Vaz ◽  
M. Sousa ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Immune Responses ◽  
Cell Viability ◽  
Cytokine Production ◽  
Cell Damage ◽  
Protoporphyrin Ix ◽  
Fold Increase ◽  
Dna Degradation ◽  
Tnf Α

Abstract Little is known regarding whether photodynamic therapy (PDT)-induced cell death can substantially compromise macrophages (MΦ), which are important cells in PDT-induced immune responses. Here, parameters of PDT-mediated MΦ cytotoxicity and cytokine production in response to protoporphyrin IX (PpIX) were evaluated. Peritoneal MΦ from BALB/c mice were stimulated in vitro with PDT, light, PpIX, or lipopolysaccharide (LPS). After that, cell viability, lipid peroxidation, Nitric Oxide (NO), DNA damage, TNF-α, IL-6 and IL-10 were evaluated. Short PDT exposure reduced cell viability by 10–30%. There was a two-fold increase in NO and DNA degradation, despite the non-increase in lipoperoxidation. PDT increased TNF-α and IL-10, particularly in the presence of LPS, and decreased the production of IL-6 to 10-fold. PDT causes cellular stress, induces NO radicals and leads to DNA degradation, generating a cytotoxic microenvironment. Furthermore, PDT modulates pro- and anti-inflammatory cytokines in MΦ.

scholarly journals Characterization of Acetaminophen Toxicity in Human Kidney HK-2 Cells

2016 ◽  
pp. 627-635 ◽  
Author(s):  
M. VRBOVÁ ◽  
E. ROUŠAROVÁ ◽  
L. BRŮČKOVÁ ◽  
P. ČESLA ◽  
T. ROUŠAR
Keyword(s):  
Cell Viability ◽  
Human Kidney ◽  
Glutathione Depletion ◽  
Secondary Site ◽  
Ros Production ◽  
Drug Induced ◽  
Acetaminophen Toxicity ◽  
Proximal Tubular ◽  
Intracellular Changes

Acetaminophen (APAP) overdose causes liver injury, but in some cases it is associated also with renal impairment. While several studies exist in relation to acetaminophen nephrotoxicity, no reports have been published describing intracellular changes related to APAP nephrotoxicity in vitro. Because proximal tubular cells are considered to constitute a secondary site of drug-induced injury after hepatocytes, our study's aim was to estimate the toxicity in the human HK-2 cell line. We used a range of APAP concentrations (1-10 mM) to examine toxicity in the cells (1-48 h). We evaluated cell viability using the WST-1 and LDH tests. Cells impairment was also determined by monitoring ROS production, glutathione levels. We proved that HK-2 cells are able to metabolize acetaminophen. We observed moderate impairment of cells already after 1 h of treatment based on a finding of increased ROS production and decreased cell viability. After 24 h, the results showed significant cellular impairment at all tested concentrations except for 1 mM APAP, but no glutathione depletion was found. We conclude that HK-2 cells are susceptible to acetaminophen toxicity but, unlike hepatocytes, it might be not linked to glutathione depletion.

scholarly journals Effect of Photodynamic Therapy on Gemcitabine-Resistant Cholangiocarcinoma in vitro and in vivo Through KLF10 and EGFR

2021 ◽  
Vol 9 ◽  
Author(s):  
Yang Yang ◽  
Jigang Li ◽  
Lei Yao ◽  
Lile Wu
Keyword(s):  
Photodynamic Therapy ◽  
Cell Viability ◽  
Promoter Region ◽  
Phase Cell ◽  
Online Data ◽  
Cycle Arrest ◽  
Egfr Expression ◽  
Cholangiocarcinoma Cell

Cholangiocarcinoma is a relatively rare neoplasm with increasing incidence. Although chemotherapeutic agent such as gemcitabine has long been used as standard treatment for cholangiocarcinoma, the interindividual variability in target and drug sensitivity and specificity may lead to therapeutic resistance. In the present study, we found that photodynamic therapy (PDT) treatment inhibited gemcitabine-resistant cholangiocarcinoma cells via repressing cell viability, enhancing cell apoptosis, and eliciting G1 cell cycle arrest through modulating Cyclin D1 and caspase 3 cleavage. In vivo, PDT treatment significantly inhibited the growth of gemcitabine-resistant cholangiocarcinoma cell-derived tumors. Online data mining and experimental analyses indicate that KLF10 expression was induced, whereas EGFR expression was downregulated by PDT treatment; KLF10 targeted the EGFR promoter region to inhibit EGFR transcription. Under PDT treatment, EGFR overexpression and KLF10 silencing attenuated the anti-cancer effects of PDT on gemcitabine-resistant cholangiocarcinoma cells by promoting cell viability, inhibiting apoptosis, and increasing S phase cell proportion. Importantly, under PDT treatment, the effects of KLF10 silencing were significantly reversed by EGFR silencing. In conclusion, PDT treatment induces KLF10 expression and downregulates EGFR expression. KLF10 binds to EGFR promoter region to inhibit EGFR transcription. The KLF10/EGFR axis participates in the process of the inhibition of PDT on gemcitabine-resistant cholangiocarcinoma cells.

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