scholarly journals Photosensitization of a subcutaneous tumour by the natural anthraquinone parietin and blue light

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
María Laura Mugas ◽  
Gustavo Calvo ◽  
Juliana Marioni ◽  
Mariela Céspedes ◽  
Florencia Martinez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Blue Light ◽  
Tumour Growth ◽  
Normal Skin ◽  
Multiple Comparisons ◽  
Leukemic Cells ◽  
Growth Delay ◽  
Cell Growth And Migration ◽  
Superficial Area

AbstractPhotodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a suitable wavelength. In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours. Photodynamic therapy mediated by parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT, *p < 0.0001, ANOVA test followed by Tukey’s multiple comparisons test), suggesting that both PTN and PTN-PDT would be potential inhibitors of metastasis. Fluorescence microscopy observation indicated cytoplasmic localization of the AQ and no fluorescence at all was recorded in the nuclei. When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28% both on days 3 and 4 of the experiment (*p < 0.05 control vs. PTN-PDT, two-way ANOVA, followed by Sidak’s multiple comparisons test). Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties. On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

scholarly journals Topical Application of the Anthraquinone Parietin and Blue Light Illumination Induces Delayed Cell Growth and Necrosis in the Deeper Layers of a Subcutaneously Implanted Tumour

2021 ◽  
Author(s):  
María Laura Mugas ◽  
Gustavo Calvo ◽  
Juliana Marioni ◽  
Mariela Céspedes ◽  
Florencia Martinez ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Cell Growth ◽  
Blue Light ◽  
Tumour Growth ◽  
Leukemic Cells ◽  
Growth Delay ◽  
Light Illumination ◽  
Cell Growth And Migration ◽  
Superficial Area

Abstract Photodynamic therapy (PDT) is an anticancer treatment involving administration of a tumour-localizing photosensitizer, followed by activation by light of a specific wavelength.In previous work, we showed that the natural anthraquinone (AQ) Parietin (PTN), was a promising photosensitizer for photodynamic therapy of leukemic cells in vitro. The present work aimed to analyze the photosensitizing ability of PTN in the mammary carcinoma LM2 cells in vitro and in vivo in a model of subcutaneously implanted tumours.Photodynamic therapy mediated by Parietin (PTN-PDT) (PTN 30 µM, 1 h and 1.78 J/cm2 of blue light) impaired cell growth and migration of LM2 cells in vitro. PTN per se induced a significant decrease in cell migration, and it was even more marked after illumination (migration index was 0.65 for PTN and 0.30 for PTN-PDT), suggesting that both PTN and parietin-mediated PDT would be potential inhibitors of metastasis.Fluorescence microscopy observation indicated cytoplasmatic localization of the AQ and no fluorescence at all was recorded in the nuclei.When PTN (1.96 mg) dissolved in dimethyl sulfoxide was topically applied on the skin of mice subcutaneously implanted with LM2 cells, PTN orange fluorescence was strongly noticed in the stratum corneum and also in the inner layers of the tumour up to approximately 5 mm. After illumination with 12.74 J/cm2 of blue light, one PDT dose at day 1, induced a significant tumour growth delay at day 3, which was not maintained in time. Therefore, we administered a second PTN-PDT boost on day 3. Under these conditions, the delay of tumour growth was 28 % both on days 3 and 4 of the experiment.Histology of tumours revealed massive tumour necrosis up to 4 mm of depth. Intriguingly, a superficial area of viable tumour in the 1 mm superficial area, and a quite conserved intact skin was evidenced. We hypothesize that this may be due to PTN aggregation in contact with the skin and tumour milieu of the most superficial tumour layers, thus avoiding its photochemical properties.On the other hand, normal skin treated with PTN-PDT exhibited slight histological changes. These preliminary findings encourage further studies of natural AQs administered in different vehicles, for topical treatment of cutaneous malignancies.

ERYTHROSINE AS A PHOTOSENSITIZER FOR ANTIMICROBIAL PHOTODYNAMIC THERAPY WITH BLUE LIGHT-EMITTING DIODES – AN IN VITRO STUDY

2021 ◽  
pp. 102445
Author(s):  
Marcela Leticia Leal Gonçalves ◽  
Elaine Marcílio Santos ◽  
Ana Cláudia Muniz Renno ◽  
Anna Carolina Ratto Tempestini Horliana ◽  
Matheus de Almeida Cruz ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Blue Light ◽  
Light Emitting Diodes ◽  
In Vitro Study ◽  
Vitro Study ◽  
Antimicrobial Photodynamic Therapy ◽  
Light Emitting

scholarly journals Staphylococcus aureus growth delay after exposure to low fluencies of blue light (470 nm)

2020 ◽  
Author(s):  
I. D. C. Galo ◽  
B. E. De Lima ◽  
T. G. Santos ◽  
A. Braoios ◽  
R. P. Prado ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Blue Light ◽  
Bacterial Infections ◽  
Growth Delay ◽  
Control Group ◽  
Prolonged Incubation ◽  
Bacterial Cultures ◽  
Experimental Approaches ◽  
Prolonged Hospital

Abstract Antibiotic resistance is one of the greatest challenges to treat bacterial infections worldwide, leading to increase in medical expenses, prolonged hospital stay and increased mortality. The use of blue light has been suggested as an innovative alternative to overcome this problem. In this study we analyzed the antibacterial effect of blue light using low emission parameters on Staphylococcus aureus cultures. In vitro bacterial cultures were used in two experimental approaches. The first approach included single or fractionated blue light application provided by LED emitters (470 nm), with the following fluencies: 16.29, 27.16 and 54.32 J/cm2. For the second approach a power LED (470 nm) was used to deliver 54.32 J/cm2 fractionated in 3 applications. Our results demonstrated that bacterial cultures exposed to fractionated blue light radiation exhibited significantly smaller sizes colonies than the control group after 24 h incubation, however the affected bacteria were able to adapt and continue to proliferate after prolonged incubation time. We could conclude that the hypothetical clinical use of low fluencies of blue light as an antibacterial treatment is risky, since its action is not definitive and proves to be ineffective at least for the strain used in this study.

scholarly journals Effect of Blue Light and Photosensitizers on Cutibacterium acnes on Shoulder Periprosthetic Joint Infection Isolates

2020 ◽  
Vol 5 (4) ◽  
pp. 187-197
Author(s):  
Swati Bhargava ◽  
Thomas Listopadzki ◽  
Sara Diletti ◽  
John K. Crane ◽  
Thomas R. Duquin ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Photodynamic Therapy ◽  
Blue Light ◽  
Periprosthetic Joint Infection ◽  
Acne Vulgaris ◽  
Joint Infection ◽  
Prosthetic Joint ◽  
Highly Sensitive ◽  
Cutibacterium Acnes

Abstract. Introduction: Cutibacterium acnes is gaining recognition as a leading pathogen after orthopaedic shoulder procedures. Photodynamic therapy, a combination of light and a photosensitizer, has demonstrated antimicrobial activity against C. acnes in the treatment of acne vulgaris. We sought to evaluate the effect of photodynamic therapy using blue light and photosensitizers on C. acnes isolates from shoulder prosthetic joint infections.Methods: C. acnes strains isolated from 19 patients with shoulder PJI were exposed to blue light alone (415 nm) or in combination with photosensitizers (fluorescein, riboflavin and demeclocycline). C. acnes strains were divided into 4 categories: Highly Sensitive (HS), Sensitive (S), Weakly Sensitive (WS), Resistant to blue light.Results: 13 of 19 C. acnes strains (68%) were S or HS to blue light alone. Of these 19 strains tested, 11 were tested with blue light and fluorescein or blue light plus riboflavin. Fluorescein (1 µg/mL) enhanced the effect of blue light in 6 of 11 strains (55%). Blue light plus riboflavin (10 µg/mL) resulted enhanced killing in 3 of 11 strains (27%), but produced a paradoxical photoprotective effect in 4 of 11 strains (36%), resulting in a net decrease compared to blue light alone. Demeclocycline, however, enhanced the effect of blue light in 16 of 17 strains (94 %).Conclusions: Blue light with the addition of photosensitizers killed C. acnes from periprosthetic shoulder infections in vitro, with demeclocycline having the most pronounced effect.

Novel Meso-substituted Porphyrin Derivatives and its Potential use in Photodynamic Therapy of Cancer

2021 ◽  
Author(s):  
Pablo Vallecorsa ◽  
Gabriela Di Venosa ◽  
M. Belén Ballatore ◽  
Dario Ferreyra ◽  
Leandro Mamone ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Normal Skin ◽  
Hair Follicles ◽  
Systemic Administration ◽  
Mammary Adenocarcinoma ◽  
Quantum Yields ◽  
High Accumulation ◽  
Photodynamic Therapy Of Cancer ◽  
Potential Use

Abstract Background: Photodynamic therapy (PDT) is an anticancer treatment that utilizes the interaction of light and a photosensitiser (PS), promoting tumour cell death mediated by generation of reactive oxygen species. In this study, we evaluated the in vitro photoactivity of four meso-substituted porphyrins and a porphyrin coupled to a fullerene. Methods: The cell line employed was the LM3 mammary adenocarcinoma, and the PS with the best photokilling activity was administered to mice bearing the LM3 subcutaneously implanted adenocarcinoma. The TEMCP4+ porphyrin and its analogue TEMCC4+ chlorine contain four identical carbazoyl substituents at the meso positions of the tetrapyrrolic macrocycle and have A4 symmetry. The TAPP derivative also has A4 symmetry, and it is substituted at the meso positions by aminopropoxy groups. The DAPP molecule has ABAB symmetry with aminopropoxy and the trifluoromethyl substituents in trans positions. The TCP-C604+ dyad is formed by a porphyrin unit covalently attached to the fullerene C60.Results: The PSs are taken up by the cells with the following efficiency: TAPP> TEMCP4+= TEMCC4+> DAPP >TCP-C604+, and the amount of intracellular PS correlates fairly with the photodamage degree, but also the quantum yields of singlet oxygen influence the PDT outcome. TAPP, DAPP, TEMCC4+ and TEMCP4+ exhibit high photoactivity against LM3 mammary carcinoma cells, being TAPP the most active. After topical application of TAPP on the skin of mice bearing LM3 tumours, the molecule is localized mainly in the stratum corneum, and at a lower extent in hair follicles and sebaceous glands. Systemic administration of TAPP produces a tumour: normal skin ratio of 31.4, and high accumulation in intestine and lung.Conclusion: The results suggest a potential use of topical TAPP for the treatment of actinic keratosis and skin adnexal neoplasms. In addition, selectivity for tumour tissue after systemic administration highlights the selectivity of and potentiality of TAPP as a new PS.

scholarly journals ITIH5, a p53-responsive gene, inhibits the growth and metastasis of melanoma cells by downregulating the transcriptional activity of KLF4

2021 ◽  
Vol 12 (5) ◽  
Author(s):  
Jia Liu ◽  
Feng Cao ◽  
Xiaojie Li ◽  
Li Zhang ◽  
Zhengrong Liu ◽  
...  
Keyword(s):  
Melanoma Cell ◽  
Transcriptional Activity ◽  
Ex Vivo ◽  
Normal Skin ◽  
Suppressor Gene ◽  
Melanoma Cells ◽  
Tumour Suppressor Gene ◽  
Cell Growth And Migration ◽  
And Migration

AbstractITIH5, a member of the inter-α-trypsin inhibitory (ITI) gene family, acts as a putative tumour-suppressor gene in many cancers. However, its role and the regulatory mechanism in melanoma are still unclear. Here, we found that the expression of ITIH5 was decreased in melanoma tissues compared with normal skin tissues. Decreased expression of ITIH5 was correlated with clinicopathological features and predicted poor prognosis in patients with melanoma. Forced expression of ITIH5 significantly inhibited melanoma cell proliferation and metastasis in vitro and ex vivo while knockdown of ITIH5 expression enhanced the malignant behaviour of melanoma cells. In further mechanistic studies, we showed that p53 can directly bind to the promoter of ITIH5 and thus promotes transcription of ITIH5 in melanoma cells. Additionally, we found that ITIH5 interacted with Krüppel-like factor 4 (KLF4) and inhibited its transcriptional activity. Collectively, our data not only identified a tumour-suppressive role of ITIH5 in melanoma but also revealed that upregulation of ITIH5 by p53 suppressed melanoma cell growth and migration likely by downmodulating the transcriptional activity of KLF4.

scholarly journals Blue Light Photodynamic Therapy With Curcumin and Riboflavin in the Management of Periodontitis: A Systematic Review

2021 ◽  
Vol 12 (1) ◽  
pp. e15-e15
Author(s):  
Ardavan Etemadi ◽  
Mehdi Hamidain ◽  
Steven Parker ◽  
Nasim Chiniforush
Keyword(s):  
Systematic Review ◽  
Photodynamic Therapy ◽  
Blue Light ◽  
Web Of Science ◽  
Scientific Literature ◽  
Bacterial Species ◽  
Antimicrobial Photodynamic Therapy ◽  
Keywords Photodynamic Therapy ◽  
Blue Wavelength

Introduction: The aim of this article was to evaluate reports in the scientific literature that used antimicrobial photodynamic therapy (aPDT) with a blue light source and curcumin and riboflavin as photosensitizers in the management of periodontitis. Methods: The search was conducted in electronic databases, including PubMed, Web of Science, and Scopus, with the keywords "photodynamic therapy", "antimicrobial photodynamic therapy", "laser activated disinfection", "photoactivated disinfection", "light activated disinfection" "LED", "Periodontitis", "Curcumin", "Riboflavin", and "periodontitis" from 2012 to 2020. Results: After evaluating a total of 24 relevant articles, 13 articles were selected, full texts were read, and the data were extracted and placed in a table. Conclusion: Reviewing articles showed that curcumin as a photosensitizer activated by a blue wavelength is effective in the elimination of the various bacterial species involved in periodontal disease, and to the best of our knowledge, there is no study that has shown this substance does not reduce bacteria. According to the result of the articles, riboflavin as a photosensitizer activated by blue light can reduce bacteria that are involved in periodontitis, but other studies have reported that blue light alone can also reduce bacteria significantly. Therefore, more in-vitro and clinical trial studies are needed to give a more conclusive opinion on the effectiveness of riboflavin as a photosensitizer in the treatment of periodontitis.

Low-dose photodynamic therapy promotes a cytotoxic immunological response in a murine model of pleural mesothelioma

2020 ◽  
Vol 58 (4) ◽  
pp. 783-791
Author(s):  
Sabrina Cavin ◽  
Aspasia Gkasti ◽  
Julien Faget ◽  
Yameng Hao ◽  
Igor Letovanec ◽  
...  
Keyword(s):  
Photodynamic Therapy ◽  
Immune Checkpoint ◽  
Tumour Growth ◽  
Low Dose ◽  
Immune Checkpoint Inhibitor ◽  
Immune Cell ◽  
Checkpoint Inhibitor ◽  
Pleural Mesothelioma ◽  
Tumour Control

Abstract OBJECTIVES Malignant pleural mesothelioma (MPM) is a deadly disease with limited treatment options. Approaches to enhance patient immunity against MPM have been tested but shown variable results. Previously, we have demonstrated interesting vascular modulating properties of low-dose photodynamic therapy (L-PDT) on MPM. Here, we hypothesized that L-PDT vascular modulation could favour immune cell extravasation in MPM and improve tumour control in combination with immune checkpoint inhibitors. METHODS First, we assessed the impact of L-PDT on vascular endothelial E-selectin expression, a key molecule for immune cell extravasation, in vitro and in a syngeneic murine model of MPM. Second, we characterized the tumour immune cell infiltrate by 15-colour flow cytometry analysis 2 and 7 days after L-PDT treatment of the murine MPM model. Third, we determined how L-PDT combined with immune checkpoint inhibitor anti-CTLA4 affected tumour growth in a murine MPM model. RESULTS L-PDT significantly enhanced E-selectin expression by endothelial cells in vitro and in vivo. This correlated with increased CD8+ T cells and activated antigen-presenting cells (CD11b+ dendritic cells and macrophages) infiltration in MPM. Also, compared to anti-CTLA4 that only affects tumour growth, the combination of L-PDT with anti-CTLA4 caused complete MPM regression in 37.5% of animals. CONCLUSIONS L-PDT enhances E-selectin expression in the MPM endothelium, which favours immune infiltration of tumours. The combination of L-PDT with immune checkpoint inhibitor anti-CTLA4 allows best tumour control and regression.

scholarly journals In vitro toxicity testing of phthalocyanines on different cell lines using a continuous laser source

2010 ◽  
Author(s):  
◽  
Kaminee Maduray
Keyword(s):  
Photodynamic Therapy ◽  
Cell Viability ◽  
Cancer Cells ◽  
Normal Skin ◽  
Light Dose ◽  
Laser Source ◽  
Normal Fibroblast ◽  
Melanoma Cancer ◽  
Skin Cells

Photodynamic therapy is a promising treatment for cancer. It involves the combination of a photosensitizer and light of an appropriate wavelength (laser source) to cause the destruction of cancer cells. Phthalocynanines are second–generation photosensitizers with enhanced photophysical and photochemical properties. In this in vitro study the effect of aluminium (AlTSPc) or zinc (ZnTSPc) tetrasulfophthalocyanines in its inactive and active state (laser induced) on melanoma (skin cancer cells), fibroblast (healthy normal skin cells) and keratinocyte (healthy normal skin cells) cells was evaluated. For each of the cell lines approximately 3 x 104 cells/ml were seeded onto 24-well cell culture plates and allowed to attach overnight, after which cells were treated with different concentrations of AlTSPc or ZnTSPc. The photosensitizers were synthesized at Rhodes University. After 2 hrs, cells were irradiated with a diode laser at a wavelength of 672 nm and a beam diameter of 1 cm. The laser power varied between 20-30 mW and the irradiation time was calculated to deliver a light dose of 4.5 J/cm2. Post-irradiated cells were incubated for 24 hrs before cell viability was measured using the CellTiter-BlueTM Viability Assay. Also, the efficacy of the light dose and laser source used for the killing of approximately 50% of the melanoma cancer cells were investigated. AlTSPc and ZnTSPc decreased cell viability of melanoma cancer cells to approximately 50% with photosensitizer concentrations of 40 μg/ml and 50 μg/ml respectively. These photosensitizer concentrations caused a slight decrease in the percentage cell viability of fibroblast and keratinocyte cells. Results for the dark toxicity assay showed that iii both photosensitizers in the presence of high concentrations (60 μg/ml – 100 μg/ml) showed cytotoxicity effects on melanoma cancer cells in their inactive state. This was not observed in fibroblast and keratinocyte cells treated under the same experimental conditions. The optimal AlTSPc and ZnTSPc concentrations in combination with the light dose of 4.5 J/cm2 was the most efficient in killing the melanoma cancer cells with reduced killing effects on healthy normal fibroblast and keratinocyte cells when compared to other light doses (2.5 J/cm2, 7.5 J/cm2 and 10 J/cm2). The irradiation of cells photosensitized with the optimal photosensitizer concentrations with a femtosecond laser using similar laser parameters to continuous wave laser experiments resulted in a reduction in the cell viability of healthy normal fibroblast and keratinocyte cells compared to melanoma cancer cells. The presence of DNA degradation on agarose gel, morphological changes like blebbing and ultrastructural changes like nucleus condensation indicated that photodynamic therapy treated melanoma cancer cells with the optimal concentrations of AlTSPc and ZnTSPc induced cell death via apoptosis. This concludes that low concentrations of AlTSPc and ZnTSPc activated with an appropriate laser source can be used to induce cell death in melanoma cancer cells. Both AlTSPc and ZnTSPc exhibit the potential to be used as a photosensitizer in photodynamic therapy for the treatment of melanoma cancer with the occurrence of minimal damage to surrounding healthy tissue.

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