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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Immunology and Immunotherapy".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 10710

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Dr. Stefano Bacci

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Research Unit of Histology and Embryology, Department of Biology, University of Florence, Florence, Italy
Interests: photobiology; photoimmunology; phototherapy; targeted therapies; photobiomodulation; wound healing; basic sciences
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Prof. Dr. Kyungsu Kang

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Principal Research Scientist, Natural Product Informatics Research Center, Korea Institute of Science and Technology (KIST), 679 Saimdang-ro, Gangneung 25451, Gangwon-do, Republic of Korea
Interests: antimicrobial photodynamic therapy; aging and longevity; bioactivity of natural products; biochemical and molecular mechanism; biophotonics; Caenorhabditis elegans model; functional foods; gut microbiome modulation; intestinal health; phytochemicals; probiotics; programmed cell death modulation by chemicals
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Dear Colleagues,

Dedicating a volume to photodynamic therapy takes on great significance because it means that many steps have been taken to understand that such therapy can take on meaning. In 1903, Von Tappeiner, Director of the Pharmacology Department of the University of Munich, in collaboration with his student, Oscar Raab, demonstrated the therapeutic action of light combined with a photosensitizer and oxygen and coined the term "photodynamic action". Since that time, many studies have experimentally verified the veracity of its effectiveness in different biological structures. In medicine, the use of photodynamic therapy (PDT) is now widely documented and well codified for the treatment of oncological and non-oncological diseases such as macular degeneration of the retina and carcinoma of the esophagus and lung. In dermatology, the use includes oncological diseases such as basal cell carcinoma and squamous cell carcinoma; actinic and non-oncological keratoses; bacterial, fungal, viral, immunological or inflammatory infections in the treatment of chronic wounds; and, finally, in cosmetology for photorejuvenation. PDT is based on the cytotoxic action of some hyperactive oxygen species, especially singlet oxygen but also superoxide anion and hydroxyl radicals, generated by the transfer of energy and/or electrons from the photoexcited oxygen sensitizer. Three important mechanisms are responsible for the efficacy of PDT: (1) the direct death of tumor cells or inflammation, (2) damage to tumor vessels, and (3) immunological response associated with the stimulation of leukocytes and the release of interleukins and other cytokines, growth factors, complement components, acute-phase proteins and other immunoregulators.

After the first successful edition, we are now launching a second volume, "Photodynamic Therapy 2.0". This new Issue continues to cover all aspects of photodynamic therapy including the discovery of new natural and synthetic photosensitizers, biomaterials and nanotechnology, in vitro and in vivo studies and clinical trials. With the collaboration of all of us, this volume will strengthen and stimulate further research.

Dr. Stefano Bacci
Prof. Dr. Kyungsu Kang
Guest Editors

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Keywords

antimicrobial photodynamic treatment
chronic wounds
inflammatory dermatoses
photobiology photochemistry
photochemotherapy
photosensitizing agents
skin cancer
oral mucosa

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Photodynamic Therapy (3rd Edition) in Biomedicines

Published Papers (9 papers)

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13 pages, 1928 KiB

Open AccessArticle

Post-Operational Photodynamic Therapy of the Tumor Bed: Comparative Analysis for Cold Knife and Laser Scalpel Resection

by Maria Shakhova, Vadim Elagin, Anton Plekhanov, Aleksandr Khilov, Daria Kurakina, Vladislav Kamensky and Mikhail Kirillin

Biomedicines 2024, 12(2), 291; https://doi.org/10.3390/biomedicines12020291 - 26 Jan 2024

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Abstract

In this paper, we report on a study regarding the efficiency of the post-operational phototherapy of the tumor bed after resection with both a cold knife and a laser scalpel in laboratory mice with CT-26 tumors. Post-operational processing included photodynamic therapy (PDT) with a topically applied chlorin-based photosensitizer (PS), performed at wavelengths of 405 or 660 nm, with a total dose of 150 J/cm². The selected design of the tumor model yielded zero recurrence in the laser scalpel group and 92% recurrence in the cold knife group without post-processing, confirming the efficiency of the laser scalpel in oncology against the cold knife. The application of PDT after the cold knife resection decreased the recurrence rate to 70% and 42% for the 405 nm and 660 nm procedures, respectively. On the other hand, the application of PDT after the laser scalpel resection induced recurrence rates of 18% and 30%, respectively, for the considered PDT performance wavelengths. The control of the penetration of PS into the tumor bed by fluorescence confocal microscopy indicated the deeper penetration of PS in the case of the cold knife, which presumably provided deeper PDT action, while the low-dose light exposure of deeper tissues without PS, presumably, stimulated tumor recurrence, which was also confirmed by the differences in the recurrence rate in the 405 and 660 nm groups. Irradiation-only light exposures, in all cases, demonstrated higher recurrence rates compared to the corresponding PDT cases. Thus, the PDT processing of the tumor bed after resection could only be recommended for the cold knife treatment and not for the laser scalpel resection, where it could induce tumor recurrence. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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18 pages, 10070 KiB

Open AccessArticle

Different Effects of Phototherapy for Rat Glioma during Sleep and Wakefulness

by Alexander Shirokov, Inna Blokhina, Ivan Fedosov, Egor Ilyukov, Andrey Terskov, Dmitry Myagkov, Dmitry Tuktarov, Maria Tzoy, Viktoria Adushkina, Daria Zlatogosrkaya, Arina Evsyukova, Valeria Telnova, Alexander Dubrovsky, Alexander Dmitrenko, Maria Manzhaeva, Valeria Krupnova, Matvey Tuzhilkin, Inna Elezarova, Nikita Navolokin, Elena Saranceva, Tatyana Iskra, Ekaterina Lykova and Oxana Semyachkina-Glushkovskaya Show full author list Hide full author list

Biomedicines 2024, 12(2), 262; https://doi.org/10.3390/biomedicines12020262 - 24 Jan 2024

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Abstract

There is an association between sleep quality and glioma-specific outcomes, including survival. The critical role of sleep in survival among subjects with glioma may be due to sleep-induced activation of brain drainage (BD), that is dramatically suppressed in subjects with glioma. Emerging evidence demonstrates that photobiomodulation (PBM) is an effective technology for both the stimulation of BD and as an add-on therapy for glioma. Emerging evidence suggests that PBM during sleep stimulates BD more strongly than when awake. In this study on male Wistar rats, we clearly demonstrate that the PBM course during sleep vs. when awake more effectively suppresses glioma growth and increases survival compared with the control. The study of the mechanisms of this phenomenon revealed stronger effects of the PBM course in sleeping vs. awake rats on the stimulation of BD and an immune response against glioma, including an increase in the number of CD8+ in glioma cells, activation of apoptosis, and blockage of the proliferation of glioma cells. Our new technology for sleep-phototherapy opens a new strategy to improve the quality of medical care for patients with brain cancer, using promising smart-sleep and non-invasive approaches of glioma treatment. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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8 pages, 566 KiB

Open AccessArticle

The Effect of Different Output Powers of Blue Diode Laser along with Curcumin and Riboflavin against Streptococcus mutans around Orthodontic Brackets: An In Vitro Study

by Edris Pordel, Trife Ghasemi, Shima Afrasiabi, Stefano Benedicenti, Antonio Signore and Nasim Chiniforush

Biomedicines 2023, 11(8), 2248; https://doi.org/10.3390/biomedicines11082248 - 10 Aug 2023

Cited by 2 | Viewed by 915

Abstract

Objectives: The aim of the present study was to determine the effects of antimicrobial photodynamic therapy (aPDT) using the blue diode laser (BDL) with different output powers and the photosensitizers riboflavin and curcumin on reducing the number of Streptococcus mutans around orthodontic brackets. Materials and methods: A total of 36 orthodontic brackets were contaminated with S. mutans and randomly assigned to 12 groups as follows: control, riboflavin alone, riboflavin + BDL with an output power of 200, 300, 400, or 500 mW, and curcumin alone, curcumin + BDL with an output power of 200, 300, 400, or 500 mW, and 0.2% chlorhexidine (CHX-positive control). Orthodontic brackets were irradiated with a BDL (wavelength 445 nm) at a power density of 0.4–1.0 W/cm² for 30 s. All orthodontic brackets were examined under a stereomicroscope at 10× magnification. Mean colony-forming units (CFUs)/mL were measured before and after treatment. A one-way analysis of variance with Tukey’s post hoc test was performed to compare CFU/mL between groups. Results: CHX and curcumin plus BDL with an output power of 500 mW had the highest reduction in S. mutans colony numbers (p < 0.001). The curcumin groups were more effective than the riboflavin groups. Riboflavin alone and riboflavin + BDL with an output power of 200 mW showed no significant difference from the control group (p = 0.99 and 0.74, respectively). Conclusion: Our results suggest that aPDT using curcumin as a photosensitizer plus BDL with an output power of 500 mW and a power density of 1.0 W/cm² at a wavelength of 445 nm can effectively reduce colonies of S. mutans around stainless steel brackets. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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9 pages, 1633 KiB

Open AccessArticle

The Evaluation of SWEEPS Plus Antimicrobial Photodynamic Therapy with Indocyanine Green in Eliminating Enterococcus faecalis Biofilm from Infected Root Canals: An In Vitro Study

by Golriz Rostami, Shima Afrasiabi, Stefano Benedicenti, Antonio Signore and Nasim Chiniforush

Biomedicines 2023, 11(7), 1850; https://doi.org/10.3390/biomedicines11071850 - 28 Jun 2023

Cited by 3 | Viewed by 973

Abstract

Objectives: This study aimed to assess the efficacy of shockwave-enhanced emission photoacoustic streaming (SWEEPS) plus antimicrobial photodynamic therapy (aPDT) using indocyanine green (ICG) for the elimination of Enterococcus faecalis biofilm from infected root canals. Materials and Methods: thirty sound human single-canal teeth were chosen and standardized to have 12 mm of root length. The root canals were shaped and prepared by means of ProTaper rotary files. After sterilization of the teeth, the canals were inoculated with E. faecalis for 2 weeks. The teeth were then randomly divided into six groups (n = five) of control, ICG, ICG + 808 nm diode laser, ICG + SWEEPS, ICG + 808 nm diode laser + SWEEPS, and 5.25% sodium hypochlorite (NaOCl). Following treatment, the number of colony-forming units (CFUs)/mL were calculated for each group. Statistical analysis was carried out using one-way ANOVA. For multiple comparisons, Tukey’s test was used as the post hoc test. Results: NaOCl alone showed the highest efficacy (p < 0.001). The ICG + 808 nm diode laser + SWEEPS group displayed significantly lower amounts of bacteria than either the ICG + 808 nm diode laser or SWEEPS (p < 0.001). There was a statistically significant difference detected between the ICG + 808 nm diode laser and ICG + SWEEPS (p = 0.035). Conclusions: SWEEPS can effectively increase the photosensitizer distribution in the root canal space, and its application along with irrigants can bring about promising results. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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12 pages, 7531 KiB

Open AccessArticle

Evaluation of the Photoactivation Effect of 3% Hydrogen Peroxide in the Disinfection of Dental Implants: In Vitro Study

by Ivan Katalinić, Igor Smojver, Luka Morelato, Marko Vuletić, Ana Budimir and Dragana Gabrić

Biomedicines 2023, 11(4), 1002; https://doi.org/10.3390/biomedicines11041002 - 24 Mar 2023

Cited by 1 | Viewed by 1529

Abstract

Photoactivation of 3% hydrogen peroxide with a 445 nm diode laser represents a relatively new, insufficiently researched antimicrobial method in the treatment of peri-implantitis. The purpose of this work is to evaluate the effect of photoactivation of 3% hydrogen peroxide with a 445 nm diode laser, and to compare the obtained results with 0.2% chlorhexidine treatment and 3% hydrogen peroxide treatment without photoactivation, in vitro, on the surface of dental implants contaminated with S. aureus and C. albicans biofilms. Previously, 80 infected titanium implants with S. aureus and C. albicans cultures were divided into four groups: G1-negative control (no treatment), G2-positive control (0.2% chlorhexidine), G3 (3% hydrogen peroxide), and G4 (photoactivated 3% hydrogen peroxide). The number of viable microbes in each sample was determined by the colony forming unit (CFU) count. The results were statistically processed and analyzed, showing a statistically significant difference across all groups compared to the negative control (G1), and the absence of a statistically significant difference between groups G1–G3. The new antimicrobial treatment, according to the results, could be worthy of further analysis and research. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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16 pages, 1427 KiB

Open AccessReview

Photodynamic Therapy for the Treatment of Bowen’s Disease: A Review on Efficacy, Non-Invasive Treatment Monitoring, Tolerability, and Cosmetic Outcome

by Paolo Antonetti, Cristina Pellegrini, Chiara Caponio, Manfredo Bruni, Lorenzo Dragone, Mirco Mastrangelo, Maria Esposito and Maria Concetta Fargnoli

Biomedicines 2024, 12(4), 795; https://doi.org/10.3390/biomedicines12040795 - 03 Apr 2024

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Abstract

Bowen’s disease represents the in situ form of cutaneous squamous cell carcinoma; although it has an excellent prognosis, 3–5% of lesions progress to invasive cutaneous squamous cell carcinoma, with a higher risk in immunocompromised patients. Treatment is therefore always necessary, and conventional photodynamic therapy is a first-line option. The aim of this review is to provide an overview of the clinical response, recurrence rates, safety, and cosmetic outcome of photodynamic therapy in the treatment of Bowen’s disease, considering different protocols in terms of photosensitizers, light source, and combination treatments. Photodynamic therapy is a valuable option for tumors at sites where wound healing is poor/delayed, in the case of multiple and/or large tumors, and where surgery would be difficult or invasive. Dermoscopy and reflectance confocal microscopy can be used as valuable tools for monitoring the therapeutic response. The treatment is generally well tolerated, with mild side effects, and is associated with a good/excellent cosmetic outcome. Periodic follow-up after photodynamic therapy is essential because of the risk of recurrence and progression to cSCC. As the incidence of keratinocyte tumors increases, the therapeutic space for photodynamic therapy will further increase. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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24 pages, 1541 KiB

Open AccessReview

Current Photodynamic Therapy for Glioma Treatment: An Update

by David Aebisher, Agnieszka Przygórzewska, Angelika Myśliwiec, Klaudia Dynarowicz, Magdalena Krupka-Olek, Andrzej Bożek, Aleksandra Kawczyk-Krupka and Dorota Bartusik-Aebisher

Biomedicines 2024, 12(2), 375; https://doi.org/10.3390/biomedicines12020375 - 06 Feb 2024

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Abstract

Research on the development of photodynamic therapy for the treatment of brain tumors has shown promise in the treatment of this highly aggressive form of brain cancer. Analysis of both in vivo studies and clinical studies shows that photodynamic therapy can provide significant benefits, such as an improved median rate of survival. The use of photodynamic therapy is characterized by relatively few side effects, which is a significant advantage compared to conventional treatment methods such as often-used brain tumor surgery, advanced radiotherapy, and classic chemotherapy. Continued research in this area could bring significant advances, influencing future standards of treatment for this difficult and deadly disease. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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14 pages, 1032 KiB

Open AccessSystematic Review

Photodynamic Therapy Can Modulate the Nasopharyngeal Carcinoma Microenvironment Infected with the Epstein–Barr Virus: A Systematic Review and Meta-Analysis

by Diógenes Germano Fornel, Túlio Morandin Ferrisse, Analú Barros de Oliveira and Carla Raquel Fontana

Biomedicines 2023, 11(5), 1344; https://doi.org/10.3390/biomedicines11051344 - 02 May 2023

Cited by 1 | Viewed by 1421

Abstract

Nasopharyngeal carcinoma is a malignancy from epithelial cells predominantly associated with the Epstein–Barr virus (EBV) infection, and it is responsible for 140,000 deaths annually. There is a current need to develop new strategies to increase the efficacy of antineoplastic treatment and reduce side effects. Thus, the present study aimed to perform a systematic review and meta-analysis of the ability of photodynamic therapy (PDT) to modulate the tumor microenvironment and PDT efficacy in nasopharyngeal carcinoma treatment. The reviewers conducted all steps in the systematic review. PubMed, Science Direct, Scopus, Scielo, Lilacs, EMBASE, and the Cochrane library databases were searched. The OHAT was used to assess the risk of bias. Meta-analysis was performed with a random-effects model (α = 0.05). Nasopharyngeal carcinoma cells treated with PDT showed that IL-8, IL-1α, IL-1β, LC3BI, LC3BII, MMP2, and MMP9 levels were significantly higher than in groups that did not receive PDT. NF-ĸB, miR BART 1-5p, BART 16, and BART 17-5p levels were significantly lower in the PDT group than in the control group. Apoptosis levels and the viability of nasopharyngeal carcinoma cells (>70%) infected with EBV were effective after PDT. This treatment also increased LMP1 levels (0.28–0.50/p < 0.05) compared to the control group. PDT showed promising results for efficacy in killing nasopharyngeal carcinoma cells infected with EBV and modulating the tumor microenvironment. Further preclinical studies should be performed to validate these results. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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6 pages, 531 KiB

Open AccessBrief Report

Methyl Aminolaevulinic Acid versus Aminolaevulinic Acid Photodynamic Therapy of Actinic Keratosis with Low Doses of Red-Light LED Illumination: Results of Long-Term Follow-Up

by Montserrat Fernández Guarino, Diego Fernández-Nieto, Laura Vila Montes and Dario de Perosanz Lobo

Biomedicines 2022, 10(12), 3218; https://doi.org/10.3390/biomedicines10123218 - 12 Dec 2022

Cited by 1 | Viewed by 1248

Abstract

Photodynamic therapy (PDT) treatment for multiple actinic keratosis (AK) has been found effective when lower doses of red light were used with methyl aminolaevulinic acid (MAL). The aim of this study was to compare the results of lower doses of red light conventional PDT (h-PDT, 16 J/cm²) with MAL and aminolaevulinic acid (ALA) in a long-term follow-up. Patients with more than five symmetrical AK on the scalp who were candidates for PDT were selected and divided randomly between MAL and ALA treatment and patients were followed at 3 and 12 months. The responses were assessed by counting the total AK and the AK per patient. Pain and adverse events were also compiled. A total of 46 patients were treated, 24 with MAL, and 22 with ALA. The two groups were comparable at baseline (p > 0.005). No significant differences were found in the results of both treatments at 12 months, despite ALA exhibiting slightly better results at 3 months. No differences in pain and adverse events were assessed. Both ALA and MAL were effective when lower doses of red light were used in c-PDT. Long term efficacy was also documented. Further studies are necessary to determine the inferior point of red-light illumination without losing efficacy. Full article

(This article belongs to the Special Issue Photodynamic Therapy 2.0)

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