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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Chemical and Molecular Sciences".

Deadline for manuscript submissions: closed (30 August 2022) | Viewed by 22153

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Assoc. Prof. Odrun Arna Gederaas

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Department of Physics, Faculty of Natural Sciences, Norwegian University of Science and Technology, Gløshaugen, NO-7491 Trondheim, Norway
Interests: Photodynamic therapy (PDT) and photochemical internalization (PCI), in vitro and in vivo experiments based on PDT and PCI. Testing of novel photosensitizers for PDT by cellular and photophysical experiments.

Dr. Gloria Mazzone

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Guest Editor

Department of Chemistry and Chemical Technologies, University of Calabria, 87036 Rende, Italy
Interests: computational chemistry; photodynamic therapy
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Special Issue Information

Dear Colleagues,

This Special Issue aims to present multidisciplinary research on photodynamic therapy (PDT) and photochemical internalization (PCI), including both in vitro and in vivo studies. Novel projects representing collaborations between chemists, biologists, physicists, engineers, and clinical academics are of particular interest, as are analyses of novel photosensitizers (cancer cell studies) in combination with modern chromatography and microscopy. Of special interest are 5-aminolevulinic based PDT (ALA-PDT) and animal glioma studies together with the development of nanoparticle-based PDT. At present, one PDT patent has been accepted (2015).

Assoc. Prof. Odrun Arna Gederaas
Dr. Gloria Mazzone
Guest Editor

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Keywords

photodynamic therapy (PDT)
photochemical internalization (PCI)
5-aminolevulinic acid (5-ALA)
photosensitizers
rat cancer models

Published Papers (6 papers)

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Research

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15 pages, 1780 KiB

Open AccessFeature PaperArticle

Computational Studies of the Photogeneration from Dihydrosanguinarine and the Probable Cytotoxicity Mechanism of Sanguinarine

by Stefano Scoditti, Simone Bruno, Emilia Sicilia and Gloria Mazzone

Appl. Sci. 2022, 12(3), 1095; https://doi.org/10.3390/app12031095 - 21 Jan 2022

Cited by 2 | Viewed by 1748

Abstract

A computational investigation of the mechanism of dihydrosanguinarine (DHSAN) photoactivation and its conversion into the active drug sanguinarine (SAN) is here reported. The reaction mechanism of DHSAN photoconversion was fully explored by considering its excitation first, essential for generating one of the reactants, the ¹O₂, and then locating all the minima and transition states involved in the formation of SAN. Both forms of the drug present at physiological pH, namely, iminium cation and alkanolamine, were considered as products of such reaction. The ability of the generated drug SAN to induce cell apoptosis was then explored, taking into consideration two anticancer activities: the induction of DNA conformational and functional changes by intercalation and the absorption of light with proper wavelength to trigger type II photochemical reactions leading to ¹O₂ sensitization for photodynamic therapy application. Concerning the ability to work as photosensitizers, the outcomes of our calculations prove that DHSAN can easily be converted into the active SAN under visible and NIR irradiation through the application of two-photon excitation, and that the maximum absorption of SAN, once intercalated into DNA, shifts to the near region of the therapeutic window. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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9 pages, 1676 KiB

Open AccessArticle

Peroxynitrite Production Induced by LPS and X-ray Treatment Enhances Cellular Incorporation of Porphyrin in Mouse RAW264 Macrophages

by Hiromu Ito

Appl. Sci. 2021, 11(8), 3503; https://doi.org/10.3390/app11083503 - 14 Apr 2021

Cited by 1 | Viewed by 1664

Abstract

Photodynamic therapy (PDT) is a minimally invasive cancer therapy that combines the accumulation of photosensitizers such as porphyrins in cancer cells with laser irradiation. I have previously reported that mitochondrially derived reactive oxygen species (ROS) regulate the expression of a porphyrin transporter, heme carrier protein 1 (HCP1), and increase porphyrin accumulation in cancer cells. Tumors that contain activated macrophages, referred to as tumor-associated macrophages (TAMs), have been reported to have increased malignancy. TAMs produce nitric oxide (NO), via the expression of inducible NO synthase (iNOS), and the highly reactive nitrogen species, peroxynitrite, which is produced by the reaction of NO with superoxide. Here, I examined the relationship between peroxynitrite, HCP1 expression, and intracellular porphyrin uptake in the murine macrophage cell line RAW264. RAW264 cells were activated by lipopolysaccharide (LPS) treatment which resulted in increased iNOS expression and NO production. Additional X-ray irradiation resulted in the generation of ROS and the subsequent generation of peroxynitrite. Importantly, LPS and X-ray co-treatment significantly enhanced HCP1 expression and porphyrin accumulation in cells, suggesting that the peroxynitrite upregulates the porphyrin transporter, HCP1. Therefore, TAMs may be effectively targeted with PDT, and tumor progression may be suppressed in general by agents that target the activation of macrophages. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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16 pages, 2218 KiB

Open AccessArticle

Considerations and Technical Pitfalls in the Employment of the MTT Assay to Evaluate Photosensitizers for Photodynamic Therapy

by Edith Alejandra Carreño, Anael Viana Pinto Alberto, Cristina Alves Magalhães de Souza, Heber Lopes de Mello, Andrea Henriques-Pons and Luiz Anastacio Alves

Appl. Sci. 2021, 11(6), 2603; https://doi.org/10.3390/app11062603 - 15 Mar 2021

Cited by 24 | Viewed by 7124

Abstract

Photodynamic therapy (PDT) combines light, a photosensitizing chemical substance, and molecular oxygen to elicit cell death and is employed in the treatment of a variety of diseases, including cancer. The development of PDT treatment strategies requires in vitro assays to develop new photosensitizers. One such assay is the MTT 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide developed in 1983 and widely used in PDT studies. Despite the exponential growth in the number of publications, a uniform MTT protocol for use in the PDT area is lacking. Herein, we list and standardize the conditions to evaluate the photosensitizer methylene blue (MB) in glioblastoma and neuroblastoma cell lines. In addition, we review technical pitfalls and identify several variables that must be taken into consideration in order to provide accurate results with MTT. We conclude that for each cell line we must have a dose-response curve using the MTT assay and good controls for the standardization. Additionally, the optimal values of the time and cell density must be in the linear range of the curve to avoid errors. We describe all relevant points and outline the best normalization techniques to observe the differences between treatments. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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9 pages, 3941 KiB

Open AccessArticle

Comparison of Two-Year Outcome of Photodynamic Therapy in Combination with Intravitreal Aflibercept or Ranibizumab for Polypoidal Choroidal Vasculopathy

by Hsin-Yu Weng, Tzu-Lun Huang, Pei-Yao Chang, Wei-Ting Ho, Yung-Ray Hsu, Fang-Ting Chen, Yun-Ju Chen and Jia-Kang Wang

Appl. Sci. 2021, 11(3), 1194; https://doi.org/10.3390/app11031194 - 28 Jan 2021

Cited by 1 | Viewed by 1330

Abstract

Purpose: To compare the two-year visual and anatomical outcomes of combination therapy of photodynamic therapy (PDT) with intravitreal aflibercept (IVA) or intravitreal ranibizumab (IVR) for patients with polypoidal choroidal vasculopathy (PCV), and to investigate the clinical factors with final visual outcome and retreatment. Methods: A retrospective medical chart review was performed for 55 eyes from 55 patients with PCV treated by a combination therapy of prompt PDT with either IVA (n = 30) or IVR (n = 25). Baseline data and treatment outcomes during the 24-month follow-up were compared between the two groups. Primary outcomes were the changes in best-corrected visual acuity (BCVA) and the rate of complete polyp regression. Secondary outcomes were the changes in central retinal thickness (CRT) and the rate of dry macula. Retreatment was administered in cases with persistent or recurrent submacular or intramacular fluid. Results: The BCVA significantly improved in the IVA/PDT group at every 6-month visit compared to the baseline. In the IVR/PDT group, there was a significant improvement of BCVA only at 6-months and 12-months, but not at 18-months and 24-months compared to the baseline. There were no significant differences in the BCVA change or CRT change between the two groups at every 6-month visit. A complete polyp regression rate at 3-months was 53.3% in IVA/PDT, and 52.0% in IVR/PDT. Significantly higher dry macula rate in Month 6 and 18 in the IVA/PDT group than in IVR/PDT group. Retreatment was performed in 26.7% patients in IVA/PDT, and in 60.0% patients in the IVR/PDT group. There were significantly lower retreatment rates in the IVA/PDT group than those in the IVR/PDT group. Better final BCVA was associated with better baseline BCVA and a younger age. Retreatment was associated with complete polyp regression at 3-months. Conclusions: Significant visual improvement was demonstrated in the IVA/PDT group at every 6-month visit, but only at a 6-month and a 12-month follow-up in the IVR/PDT group. Although changes of the BCVA/CRT and complete polyp regression rate were comparable between two groups, the IVA/PDT group required less retreatment and attained more dry macula results. Better baseline BCVA and younger age were associated with a better visual outcome. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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Review

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21 pages, 5455 KiB

Open AccessReview

Recent Development of Heavy Atom-Free Triplet Photosensitizers for Photodynamic Therapy

by Xiao Xiao, Kaiyue Ye, Muhammad Imran and Jianzhang Zhao

Appl. Sci. 2022, 12(19), 9933; https://doi.org/10.3390/app12199933 - 2 Oct 2022

Cited by 12 | Viewed by 2981

Abstract

Photodynamic therapy (PDT) is an attractive method for cancer treatment. Triplet photosensitizers (PSs) are critical for this method; upon photoexcitation, efficient intersystem crossing (ISC) occurs for triplet PSs, the triplet-excited state of the triplet PSs is populated, then via intermolecular triplet energy transfer, the O₂, in triplet-spin multiplicity at ground state, is sensitized to the singlet-excited state, i.e., singlet oxygen (¹O₂) is produced. This strong reactive oxygen species (ROS) will oxidize the biomolecules in the tumor tissue. Thus, the design of novel triplet PSs as efficient PDT agents is vital. In this review article, we will introduce the recent development of the heavy atom-free triplet PSs used for PDT, including those based on spin-orbit charge transfer ISC (SOCT-ISC), twisting of the π-conjugation framework-induced ISC, radical enhanced ISC, and thionated carbonyl-induced ISC. The ISC mechanisms and molecular structure design rationales are discussed. The less studied electron spin selectivity of the ISC of the triplet PSs is also introduced. This information is helpful for the future design of new efficient triplet PSs for PDT. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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20 pages, 4474 KiB

Open AccessReview

Advancing Photodynamic Therapy for Endodontic Disinfection with Nanoparticles: Present Evidence and Upcoming Approaches

by Rayyan A. Alfirdous, Isadora M. Garcia, Abdulrahman A. Balhaddad, Fabrício M. Collares, Frederico C. Martinho and Mary Anne S. Melo

Appl. Sci. 2021, 11(11), 4759; https://doi.org/10.3390/app11114759 - 22 May 2021

Cited by 9 | Viewed by 6281

Abstract

The persistence of microorganisms in the root canal system is one of the leading causes of root canal treatment failure. Root canal anatomy is complex, and it is often a challenge to obtain optimal disinfection. Biofilms of putative pathogens hidden inside dentin tubules and other root canal ramifications may limit current disinfection protocols. The search for additional disinfection of the root canal has been intensely carried out over the last twenty years. Antimicrobial photodynamic therapy (aPDT) is an adjunctive, conservative, non-selective bacterial kill approach. aPDT has been used to improve root canals disinfection without inducing bacterial resistance. This review focuses on the up-to-date aPDT performance and upcoming promising strategies for disinfection of the root canal system. First, we summarized the barriers encountered by photosensitizer (PS) and light delivery applied to root canal disinfection. Second, we compile the most updated clinical literature. A systematic search for scientific articles was conducted in PubMed, MEDLINE, SCOPUS, and EMBASE to screen the related in vivo studies about this theme. Third, we summarized and critically analyzed the current developments to overcome the aPDT limitations, and we revealed upcoming perspectives in this scoping literature review. We present a timely and opportune review article focusing on the significant potential of aPDT in endodontic disinfection. aPDT offers multiple capabilities that may be considered toward the root canal system’s disinfection with future outlooks in nanosized-platforms’ design and performance. Full article

(This article belongs to the Special Issue Photochemistry and Photodynamics)

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