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Pharmaceuticals
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Photodynamic Therapy 2019
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Photodynamic Therapy 2019

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 July 2019) | Viewed by 41454

Special Issue Editor

Prof. Dr. Serge Mordon

E-Mail Website1 Website2
Guest Editor
INSERM (French National Institute of Health and Medical Research) U1026, The Laboratory of the Bioengineering of Tissues (BioTis), University of Bordeaux, 146 rue Léo Saignat, 33076 Bordeaux, France
Interests: photodynamic therapy; cancer; clinical evaluation; photosensitizer; dosimetry; fluorescencer; Dosimetry; fluorescence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a light-based photochemistry process. The illumination of a photoactivatable molecule (also called photosensitizer) with visible or near infrared light produces reactive oxygen toxic species to destroy tumor cells. This treatment modality leads to highly targeted actions, because reactive oxygen species are produced only where light is applied. Light is not harmful, nor is the photoactivable molecule. Only the combination of three elements (photosensitizer, oxygen, and light) is required to induce photo-oxidation reactions. PDT has proven to be a promising modality in many medical applications including cutaneous condition, infectious diseases, and various cancers at different stages.

The journal Pharmaceuticals invites both reviews and original articles shedding light on the challenges and opportunities of the development of innovative solutions for photodynamic therapy. Topics include selective photoactivatable molecules targeting receptors over-expressed into tumors membranes and/or on neovessels; molecules exhibiting red shifted absorption for better penetration of light into the tissues, photobactericidal agents, theranostics, and photodiagnosis. Reviews and original articles dealing with PDT-associated immunotherapy , new radiation systems such as X-rays, or new devices allowing for better illumination and /or dosimetry are also welcome.

Prof. Serge Mordon
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Pharmaceuticals is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2900 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • photodynamic therapy
  • photosensitizers
  • photodiagnosis
  • cells
  • receptors
  • antimicrobial photodynamic therapy
  • fluorescence
  • X-rays
  • immunomodulation
  • light
  • dosimetry

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Published Papers (7 papers)

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Research

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9 pages, 3589 KiB  
Article
TLD1433-Mediated Photodynamic Therapy with an Optical Surface Applicator in the Treatment of Lung Cancer Cells In Vitro
by Sarah Chamberlain, Houston D. Cole, John Roque III, David Bellnier, Sherri A. McFarland and Gal Shafirstein
Pharmaceuticals 2020, 13(7), 137; https://doi.org/10.3390/ph13070137 - 28 Jun 2020
Cited by 30 | Viewed by 6749
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 [...] Read more.
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. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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18 pages, 4494 KiB  
Article
Antimicrobial Photodynamic Therapy in Combination with Nystatin in the Treatment of Experimental Oral Candidiasis Induced by Candida albicans Resistant to Fluconazole
by Karem Janeth Rimachi Hidalgo, Juliana Cabrini Carmello, Cláudia Carolina Jordão, Paula Aboud Barbugli, Carlos Alberto de Sousa Costa, Ewerton Garcia de Oliveira Mima and Ana Claudia Pavarina
Pharmaceuticals 2019, 12(3), 140; https://doi.org/10.3390/ph12030140 - 18 Sep 2019
Cited by 29 | Viewed by 4917
Abstract
Background: It has been demonstrated that azole-resistant strains of Candida albicans have a greater resistance to antimicrobial photodynamic therapy (aPDT) when compared to their more susceptible counterparts. For this reason, the present study evaluated the efficacy of aPDT, together with nystatin (NYS), in [...] Read more.
Background: It has been demonstrated that azole-resistant strains of Candida albicans have a greater resistance to antimicrobial photodynamic therapy (aPDT) when compared to their more susceptible counterparts. For this reason, the present study evaluated the efficacy of aPDT, together with nystatin (NYS), in the treatment of oral candidiasis in vivo. Methods: Mice were infected with fluconazole-resistant C. albicans (ATCC 96901). To perform the combined therapy, aPDT, mediated by Photodithazine (PDZ) and LED light, was used together with NYS. The efficacy of the treatments was evaluated by microbiological, macroscopic, histopathological and Confocal Scanning Laser Microscopy analyses of the lesions. The expression of p21 and p53, proteins associated with cell death, from the tongues of mice, was also performed. Results: The combined therapy reduced the fungal viability by around 2.6 log10 and decreased the oral lesions and the inflammatory reaction. Additionally, it stimulated the production of p53 and p21. Conclusions: The combined therapy is a promising alternative treatment for oral candidiasis induced by C. albicans resistant to fluconazole. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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11 pages, 4461 KiB  
Article
Long Term Effectiveness of Photodynamic Therapy for CIN Treatment
by Natalia Mayumi Inada, Hilde Harb Buzzá, Marieli Fernanda Martins Leite, Cristina Kurachi, Jose Roberto Trujillo, Cynthia Aparecida de Castro, Fernanda Mansano Carbinatto, Welington Lombardi and Vanderlei Salvador Bagnato
Pharmaceuticals 2019, 12(3), 107; https://doi.org/10.3390/ph12030107 - 12 Jul 2019
Cited by 36 | Viewed by 5774
Abstract
(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of [...] Read more.
(1) Background: Cervical cancer is the third most commonly diagnosed cancer and the fourth leading cause of cancer death in women worldwide. The highest incidence rates are in Africa, followed by South-Central Asia and South America. According to the Brazilian National Institute of Cancer (INCA), 16,370 new cases of cervical cancer were estimated for each year of the biennium of 2018–2019. About 90% of cervical cancers originate from the malignant progression of cervical intraepithelial neoplasia (CIN) which is classified based on cytohistological characteristics (low- and high-grade lesions). The present study reports the long-term effectiveness of topical photodynamic therapy (PDT) for CIN grades 1 and 2/3 with up to two years of follow up. (2) Methods: A total of 56 patients with CIN 1, ten with CIN 2, and 14 patients for the placebo group were enrolled in this study. (3) Results: 75% (n = 42) of CIN 1 patients presented a complete response to PDT and only 23.2% (n = 13) of recurrence, progression, and/or lesions remaining two years after PDT. For CIN 2/3 patients, 90% were observed to be cured after one and two years of follow up. (4) Conclusions: PDT presented best results two years after a non-invasive, fast, and low-cost procedure and in comparison with the placebo group, preventing the progression of cervical intraepithelial neoplasia and preserving the cervix. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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11 pages, 3500 KiB  
Article
Raman Microspectroscopy as a Tool to Elucidate the Efficacy of Topical Formulations Containing Curcumin
by Ievgeniia Iermak, Ana Paula da Silva, Cristina Kurachi, Vanderlei Salvador Bagnato and Natalia Mayumi Inada
Pharmaceuticals 2019, 12(1), 44; https://doi.org/10.3390/ph12010044 - 23 Mar 2019
Cited by 6 | Viewed by 3613
Abstract
The success of the onychomycosis treatment is directly associated with factors such as the choice of the medication, the administration route, and the pharmaceutical formulation. Photodynamic therapy (PDT) is an emerging and promising technique indicated for onychomycosis treatment. For this application, the main [...] Read more.
The success of the onychomycosis treatment is directly associated with factors such as the choice of the medication, the administration route, and the pharmaceutical formulation. Photodynamic therapy (PDT) is an emerging and promising technique indicated for onychomycosis treatment. For this application, the main challenge is the efficient delivery of the photosensitizer (PS). Curcumin is widely used as a PS, however it is an unstable molecule and it is a challenge to develop a formulation with good penetration into the nail plate, maintaining the stability of curcumin. In this study, the molecular mechanisms underlying the efficacy of two topical formulations containing curcumin used in a clinical trial for onychomycosis treatment were analyzed by Raman microspectroscopy. It is shown that curcumin is present in both formulations in aggregated and non-aggregated states, and in aggregates it is present in different conformations, depending on the interaction with the solvent. This proves to be critical for efficient and uniform PS delivery to the nail and its complete use during the treatment. These analyses are showing how promising Raman microspectroscopy is in understanding the molecular mechanisms of the efficiency of photosensitizers and are helping to improve the development of pharmaceutical formulations. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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Review

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115 pages, 18888 KiB  
Review
Fighting Hypoxia to Improve PDT
by Ludivine Larue, Bauyrzhan Myrzakhmetov, Amina Ben-Mihoub, Albert Moussaron, Noémie Thomas, Philippe Arnoux, Francis Baros, Régis Vanderesse, Samir Acherar and Céline Frochot
Pharmaceuticals 2019, 12(4), 163; https://doi.org/10.3390/ph12040163 - 30 Oct 2019
Cited by 133 | Viewed by 10444
Abstract
Photodynamic therapy (PDT) has drawn great interest in recent years mainly due to its low side effects and few drug resistances. Nevertheless, one of the issues of PDT is the need for oxygen to induce a photodynamic effect. Tumours often have low oxygen [...] Read more.
Photodynamic therapy (PDT) has drawn great interest in recent years mainly due to its low side effects and few drug resistances. Nevertheless, one of the issues of PDT is the need for oxygen to induce a photodynamic effect. Tumours often have low oxygen concentrations, related to the abnormal structure of the microvessels leading to an ineffective blood distribution. Moreover, PDT consumes O2. In order to improve the oxygenation of tumour or decrease hypoxia, different strategies are developed and are described in this review: (1) The use of O2 vehicle; (2) the modification of the tumour microenvironment (TME); (3) combining other therapies with PDT; (4) hypoxia-independent PDT; (5) hypoxia-dependent PDT and (6) fractional PDT. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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19 pages, 1800 KiB  
Review
The Dark Side: Photosensitizer Prodrugs
by Sara Sansaloni-Pastor, Jordan Bouilloux and Norbert Lange
Pharmaceuticals 2019, 12(4), 148; https://doi.org/10.3390/ph12040148 - 4 Oct 2019
Cited by 21 | Viewed by 4955
Abstract
Photodynamic therapy (PDT) and photodiagnosis (PD) are essential approaches in the field of biophotonics. Ideally, both modalities require the selective sensitization of the targeted disease in order to avoid undesired phenomena such as the destruction of healthy tissue, skin photosensitization, or mistaken diagnosis. [...] Read more.
Photodynamic therapy (PDT) and photodiagnosis (PD) are essential approaches in the field of biophotonics. Ideally, both modalities require the selective sensitization of the targeted disease in order to avoid undesired phenomena such as the destruction of healthy tissue, skin photosensitization, or mistaken diagnosis. To a large extent, the occurrence of these incidents can be attributed to “background” accumulation in non-target tissue. Therefore, an ideal photoactive compound should be optically silent in the absence of disease, but bright in its presence. Such requirements can be fulfilled using innovative prodrug strategies targeting disease-associated alterations. Here we will summarize the elaboration, characterization, and evaluation of approaches using polymeric photosensitizer prodrugs, nanoparticles, micelles, and porphysomes. Finally, we will discuss the use of 5-aminolevulinc acid and its derivatives that are selectively transformed in neoplastic cells into photoactive protoporphyrin IX. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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15 pages, 1668 KiB  
Review
Measuring Daylight: A Review of Dosimetry in Daylight Photodynamic Therapy
by Paul O’Mahoney, Marina Khazova, Ewan Eadie and Sally Ibbotson
Pharmaceuticals 2019, 12(4), 143; https://doi.org/10.3390/ph12040143 - 20 Sep 2019
Cited by 14 | Viewed by 3667
Abstract
Successful daylight photodynamic therapy (DPDT) relies on the interaction of light, photosensitisers and oxygen. Therefore, the ‘dose’ of light that a patient receives during treatment is a clinically relevant quantity, with a minimum dose for effective treatment recommended in the literature. However, there [...] Read more.
Successful daylight photodynamic therapy (DPDT) relies on the interaction of light, photosensitisers and oxygen. Therefore, the ‘dose’ of light that a patient receives during treatment is a clinically relevant quantity, with a minimum dose for effective treatment recommended in the literature. However, there are many different light measurement methods used in the published literature, which may lead to confusion surrounding reliable and traceable dose measurement in DPDT, and what the most appropriate method of light measurement in DPDT might be. Furthermore, for the majority of practitioners who do not carry out any formal dosimetry and for the patients receiving DPDT, building confidence in the evidence supporting this important treatment option is of key importance. This review seeks to clarify the methodology of DPDT and discusses the literature relating to DPDT dosimetry. Full article
(This article belongs to the Special Issue Photodynamic Therapy 2019)
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