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Insights into Photodynamic Therapy

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: closed (31 December 2019) | Viewed by 48019

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Special Issue Editors

Dr. Chin-Tin Chen

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Guest Editor

Department of Biochemical Science and Technology, National Taiwan University, No. 1, Sec. 4, Roosevelt Road, Taipei 10617, Taiwan
Interests: photodynamic therapy; drug delivery system; cell biology
Special Issues, Collections and Topics in MDPI journals

Assist. Prof. Hsuan-Chen Wu

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Guest Editor

Department of Biochemical Science and Technology, National Taiwan University, Taipei 106, Taiwan
Interests: Synthetic Biology; Biofabrication; Biotechnology

Special Issue Information

Dear Colleagues,

It is well acknowledged that photodynamic therapy (PDT), combining photosensitizer and light irradiation, has been developed as an alternative approach for treating cancers, infections, and a range of other diseases. Over the last 40 years, there has been much progress in developing photosensitizers and related delivery systems, understanding the mechanistic mechanisms in cellular responses and their influences on the immune response, and designing clinical trials for various diseases. Recently, combining PDT and other therapies has been shown to achieve better therapeutic outcomes in disease management.

This Special Issue, “Insights into Photodynamic Therapy”, will focus on experimental papers, up-to-date review articles, and commentaries that can provide molecular insights in the field of photodynamic therapy and photodynamic inactivation. Combined strategies of PDT and other therapies, are especially, but not exclusively, welcome for this Specific Issue. Authors are invited to submit manuscripts that relate to the molecular aspects of basic biology and clinical research in photodynamic therapy. The results from these articles may provide pivotal information for our understanding of PDT biology and for devising clinical strategies that may enhance the development of photodynamic medicine.

Assist. Prof. Hsuan-Chen Wu
Prof. Chin-Tin Chen
Guest Editors

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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. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

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Keywords

Photodynamic therapy
Photodynamic inactivation
Cancer
Infections
Combinational therapy

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Published Papers (10 papers)

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17 pages, 2188 KiB

Open AccessArticle

Epigallocatechin Gallate Enhances MAL-PDT Cytotoxic Effect on PDT-Resistant Skin Cancer Squamous Cells

by Daniela León, Kurt Buchegger, Ramón Silva, Ismael Riquelme, Tamara Viscarra, Bárbara Mora-Lagos, Louise Zanella, Fabiola Schafer, Cristina Kurachi, Juan Carlos Roa, Carmen Ili and Priscilla Brebi

Int. J. Mol. Sci. 2020, 21(9), 3327; https://doi.org/10.3390/ijms21093327 - 8 May 2020

Cited by 15 | Viewed by 3597

Abstract

Photodynamic therapy (PDT) has been used to treat certain types of non-melanoma skin cancer with promising results. However, some skin lesions have not fully responded to this treatment, suggesting a potential PDT-resistant phenotype. Therefore, novel therapeutic alternatives must be identified that improve PDT in resistant skin cancer. In this study, we analyzed the cell viability, intracellular protoporphyrin IX (PpIX) content and subcellular localization, proliferation profile, cell death, reactive oxygen species (ROS) detection and relative gene expression in PDT-resistant HSC-1 cells. PDT-resistant HSC-1 cells show a low quantity of protoporphyrin IX and low levels of ROS, and thus a low rate of death cell. Furthermore, the resistant phenotype showed a downregulation of HSPB1, SLC15A2, FECH, SOD2 and an upregulation of HMBS and BIRC5 genes. On the other hand, epigallocatechin gallate catechin enhanced the MAL-PDT effect, increasing levels of protoporphyrin IX and ROS, and killing 100% of resistant cells. The resistant MAL-PDT model of skin cancer squamous cells (HSC-1) is a reliable and useful tool to understand PDT cytotoxicity and cellular response. These resistant cells were successfully sensitized with epigallocatechin gallate catechin. The in vitro epigallocatechin gallate catechin effect as an enhancer of MAL-PDT in resistant cells is promising in the treatment of difficult skin cancer lesions. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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16 pages, 3773 KiB

Open AccessArticle

Genetic Aberrations Associated with Photodynamic Therapy in Colorectal Cancer Cells

by Heidi Abrahamse and Nicolette Nadene Houreld

Int. J. Mol. Sci. 2019, 20(13), 3254; https://doi.org/10.3390/ijms20133254 - 2 Jul 2019

Cited by 18 | Viewed by 3071

Abstract

Photodynamic therapy (PDT) is a cancer treatment modality that utilizes three components: light (λ 650–750 nm), a photosensitizer (PS) and molecular oxygen, which upon activation renders the modality effective. Colorectal cancer has one of the highest incident rates as well as a high mortality rate worldwide. In this study, a zinc (Zn) metal-based phthalocyanine (ZnPcSmix) PS was used to determine its efficacy for the treatment of colon adenocarcinoma cells (DLD-1 and Caco-2). Photoactivation of the PS was achieved by laser irradiation at a wavelength of 680 nm. Dose responses were performed to establish optimal PS concentration and irradiation fluence. A working combination of 20 µM ZnPcSmix and 5 J/cm² was used. Biochemical responses were determined after 1 or 24 h incubation post-treatment. Since ZnPcSmix is localized in lysosomes and mitochondria, mitochondrial destabilization analysis was performed monitoring mitochondrial membrane potential (MMP). Cytosolic acidification was determined measuring hydrogen peroxide (H₂O₂) levels in the cytoplasm. Having established apoptotic cell death induction, an apoptosis PCR array was performed to establish the apoptotic mechanism. In DLD-1 cells, expression of genes included 3 up-regulated and 20 down-regulated genes while in Caco-2 cells, there were 16 up-regulated and 22 down-regulated genes. In both cell lines, in up-regulated genes, there was a combination of pro- and anti-apoptotic genes that were significantly expressed. Gene expression results showed that more tumorigenic cells (DLD-1) went through apoptosis; however, they exhibit increased risk of resistance and recurrence, while less tumorigenic Caco-2 cells responded better to PDT, thus being suggestive of a better prognosis post-PDT treatment. In addition, the possible apoptotic mechanisms of cell death were deduced based on the genetic expression profiling of regulatory apoptotic inducing factors. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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14 pages, 3588 KiB

Open AccessArticle

Dark Antibacterial Activity of Rose Bengal

by Faina Nakonechny, Margarita Barel, Arad David, Simor Koretz, Boris Litvak, Elena Ragozin, Ariel Etinger, Oz Livne, Yosef Pinhasi, Gary Gellerman and Marina Nisnevitch

Int. J. Mol. Sci. 2019, 20(13), 3196; https://doi.org/10.3390/ijms20133196 - 29 Jun 2019

Cited by 27 | Viewed by 5165

Abstract

The global spread of bacterial resistance to antibiotics promotes a search for alternative approaches to eradication of pathogenic bacteria. One alternative is using photosensitizers for inhibition of Gram-positive and Gram-negative bacteria under illumination. Due to low penetration of visible light into tissues, applications of photosensitizers are currently limited to treatment of superficial local infections. Excitation of photosensitizers in the dark can be applied to overcome this problem. In the present work, dark antibacterial activity of the photosensitizer Rose Bengal alone and in combination with antibiotics was studied. The minimum inhibitory concentrations (MIC) value of Rose Bengal against S. aureus dropped in the presence of sub-MIC concentrations of ciprofloxacin, levofloxacin, methicillin, and gentamicin. Free Rose Bengal at sub-MIC concentrations can be excited in the dark by ultrasound at 38 kHz. Rose Bengal immobilized onto silicon showed good antibacterial activity in the dark under ultrasonic activation, probably because of Rose Bengal leaching from the polymer during the treatment. Exposure of bacteria to Rose Bengal in the dark under irradiation by electromagnetic radio frequency waves in the 9 to 12 GHz range caused a decrease in the bacterial concentration, presumably due to resonant absorption of electromagnetic energy, its transformation into heat and subsequent excitation of Rose Bengal. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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24 pages, 5462 KiB

Open AccessArticle

Novel Insights into the Effect of Hyperforin and Photodynamic Therapy with Hypericin on Chosen Angiogenic Factors in Colorectal Micro-Tumors Created on Chorioallantoic Membrane

by Martin Majerník, Rastislav Jendželovský, Marián Babinčák, Ján Košuth, Juraj Ševc, Zuzana Tonelli Gombalová, Zuzana Jendželovská, Monika Buríková and Peter Fedoročko

Int. J. Mol. Sci. 2019, 20(12), 3004; https://doi.org/10.3390/ijms20123004 - 19 Jun 2019

Cited by 21 | Viewed by 4219

Abstract

Photodynamic therapy with hypericin (HY-PDT) and hyperforin (HP) could be treatment modalities for colorectal cancer (CRC), but evidence of their effect on angiogenic factors in CRC is missing. Convenient experimental model utilization is essential for angiogenesis research. Therefore, not only 2D cell models, but also 3D cell models and micro-tumors were used and compared. The micro-tumor extent and interconnection with the chorioallantoic membrane (CAM) was determined by histological analyses. The presence of proliferating cells and HY penetration into the tumor mass were detected by fluorescence microscopy. The metabolic activity status was assessed by an colorimetric assay for assessing cell metabolic activity (MTT assay) and HY accumulation was determined by flow cytometry. Pro-angiogenic factor expression was determined by Western blot and quantitative real-time polymerase chain reaction (RT-qPCR). We confirmed the cytotoxic effect of HY-PDT and HP and showed that their effect is influenced by structural characteristics of the experimental model. We have pioneered a method for analyzing the effect of HP and cellular targeted HY-PDT on pro-angiogenic factor expression in CRC micro-tumors. Despite the inhibitory effect of HY-PDT and HP on CRC, the increased expression of some pro-angiogenic factors was observed. We also showed that CRC experimental micro-tumors created on quail CAM could be utilized for analyses of gene and protein expression. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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15 pages, 5334 KiB

Open AccessArticle

Epigenetic Alterations Induced by Photothrombotic Stroke in the Rat Cerebral Cortex: Deacetylation of Histone h3, Upregulation of Histone Deacetylases and Histone Acetyltransferases

by Svetlana Demyanenko and Anatoly Uzdensky

Int. J. Mol. Sci. 2019, 20(12), 2882; https://doi.org/10.3390/ijms20122882 - 13 Jun 2019

Cited by 14 | Viewed by 3673

Abstract

Ischemic penumbra that surrounds a stroke-induced infarction core is potentially salvageable; however, mechanisms of its formation are not well known. Covalent modifications of histones control chromatin conformation, gene expression and protein synthesis. To study epigenetic processes in ischemic penumbra, we used photothrombotic stroke (PTS), a stroke model in which laser irradiation of the rat brain cortex photosensitized by Rose Bengal induces local vessel occlusion. Immunoblotting and immunofluorescence microscopy showed decrease in acetylation of lysine 9 in histone H3 in penumbra at 1, 4 or 24 h after PTS. This was associated with upregulation of histone deacetylases HDAC1 and HDAC2, but not HDAC4, which did not localize in the nuclei. HDAC2 was found in cell nuclei, HDAC4 in the cytoplasm and HDAC1 both in nuclei and cytoplasm. Histone acetyltransferases HAT1 and PCAF (p300/CBP associated factor) that acetylated histone H3 synthesis were also upregulated, but lesser and later. PTS increased localization of HDAC2 and HAT1 in astroglia. Thus, the cell fate in PTS-induced penumbra is determined by the balance between opposite tendencies leading either to histone acetylation and stimulation of gene expression, or to deacetylation and suppression of transcriptional processes and protein biosynthesis. These epigenetic proteins may be the potential targets for anti-stroke therapy. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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10 pages, 1738 KiB

Open AccessCommunication

Efficient Photodynamic Therapy of Prostate Cancer Cells through an Improved Targeting of the Cation-Independent Mannose 6-Phosphate Receptor

by Elise Bouffard, Chiara Mauriello Jimenez, Khaled El Cheikh, Marie Maynadier, Ilaria Basile, Laurence Raehm, Christophe Nguyen, Magali Gary-Bobo, Marcel Garcia, Jean-Olivier Durand and Alain Morère

Int. J. Mol. Sci. 2019, 20(11), 2809; https://doi.org/10.3390/ijms20112809 - 8 Jun 2019

Cited by 23 | Viewed by 4247

Abstract

The aim of the present work is the development of highly efficient targeting molecules to specifically address mesoporous silica nanoparticles (MSNs) designed for the photodynamic therapy (PDT) of prostate cancer. We chose the strategy to develop a novel compound that allows the improvement of the targeting of the cation-independent mannose 6-phosphate receptor, which is overexpressed in prostate cancer. This original sugar, a dimannoside-carboxylate (M6C-Man) grafted on the surface of MSN for PDT applications, leads to a higher endocytosis and thus increases the efficacy of MSNs. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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21 pages, 5484 KiB

Open AccessArticle

New Materials Based on Cationic Porphyrins Conjugated to Chitosan or Titanium Dioxide: Synthesis, Characterization and Antimicrobial Efficacy

by Kelly A. D. F. Castro, Nuno M. M. Moura, Flávio Figueira, Rosalina I. Ferreira, Mário M. Q. Simões, José A. S. Cavaleiro, M. Amparo F. Faustino, Armando J. D. Silvestre, Carmen S. R. Freire, João P. C. Tomé, Shirley Nakagaki, A. Almeida and M. Graça P. M. S. Neves

Int. J. Mol. Sci. 2019, 20(10), 2522; https://doi.org/10.3390/ijms20102522 - 22 May 2019

Cited by 49 | Viewed by 4839

Abstract

The post-functionalization of 5,10,15-tris(1-methylpyridinium-4-yl)-20-(pentafluorophenyl)porphyrin tri-iodide, known as a highly efficient photosensitizer (PS) for antimicrobial photodynamic therapy (aPDT), in the presence of 3- or 4-mercaptobenzoic acid, afforded two new tricationic porphyrins with adequate carboxylic pending groups to be immobilized on chitosan or titanium oxide. The structural characterization of the newly obtained materials confirmed the success of the porphyrin immobilization on the solid supports. The photophysical properties and the antimicrobial photodynamic efficacy of the non-immobilized porphyrins and of the new conjugates were evaluated. The results showed that the position of the carboxyl group in the mercapto units or the absence of these substituents in the porphyrin core could modulate the action of the photosensitizer towards the bioluminescent Gram-negative Escherichia coli bacterium. The antimicrobial activity was also influenced by the interaction between the photosensitizer and the type of support (chitosan or titanium dioxide). The new cationic porphyrins and some of the materials were shown to be very stable in PBS and effective in the photoinactivation of E. coli bacterium. The physicochemical properties of TiO₂ allowed the interaction of the PS with its surface, increasing the absorption profile of TiO₂, which enables the use of visible light, inactivating the bacteria more efficiently than the corresponding PS immobilized on chitosan. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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Review

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16 pages, 854 KiB

Open AccessReview

Effect of Photodynamic Therapy on Microorganisms Responsible for Dental Caries: A Systematic Review and Meta-Analysis

by Analú Barros de Oliveira, Túlio Morandin Ferrisse, Raquel Souza Marques, Sarah Raquel de Annunzio, Fernanda Lourenção Brighenti and Carla Raquel Fontana

Int. J. Mol. Sci. 2019, 20(14), 3585; https://doi.org/10.3390/ijms20143585 - 23 Jul 2019

Cited by 71 | Viewed by 5948

Abstract

The aim of this study was to perform a systematic review of the literature followed by a meta-analysis about the efficacy of photodynamic therapy (PDT) on the microorganisms responsible for dental caries. The research question and the keywords were constructed according to the PICO strategy. The article search was done in Embase, Lilacs, Scielo, Medline, Scopus, Cochrane Library, Web of Science, Science Direct, and Pubmed databases. Randomized clinical trials and in vitro studies were selected in the review. The study was conducted according the PRISMA guideline for systematic review. A total of 34 articles were included in the qualitative analysis and four articles were divided into two subgroups to perform the meta-analysis. Few studies have achieved an effective microbial reduction in microorganisms associated with the pathogenesis of dental caries. The results highlight that there is no consensus about the study protocols for PDT against cariogenic microorganisms, although the results showed the PDT could be a good alternative for the treatment of dental caries. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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35 pages, 3313 KiB

Open AccessReview

Seeing Better and Going Deeper in Cancer Nanotheranostics

by Maharajan Sivasubramanian, Yao Chen Chuang, Nai-Tzu Chen and Leu-Wei Lo

Int. J. Mol. Sci. 2019, 20(14), 3490; https://doi.org/10.3390/ijms20143490 - 16 Jul 2019

Cited by 17 | Viewed by 4734

Abstract

Biomedical imaging modalities in clinical practice have revolutionized oncology for several decades. State-of-the-art biomedical techniques allow visualizing both normal physiological and pathological architectures of the human body. The use of nanoparticles (NP) as contrast agents enabled visualization of refined contrast images with superior resolution, which assists clinicians in more accurate diagnoses and in planning appropriate therapy. These desirable features are due to the ability of NPs to carry high payloads (contrast agents or drugs), increased in vivo half-life, and disease-specific accumulation. We review the various NP-based interventions for treatments of deep-seated tumors, involving “seeing better” to precisely visualize early diagnosis and “going deeper” to activate selective therapeutics in situ. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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21 pages, 2370 KiB

Open AccessReview

Photosensitizers Used in the Photodynamic Therapy of Rheumatoid Arthritis

by Manuel Gallardo-Villagrán, David Yannick Leger, Bertrand Liagre and Bruno Therrien

Int. J. Mol. Sci. 2019, 20(13), 3339; https://doi.org/10.3390/ijms20133339 - 7 Jul 2019

Cited by 51 | Viewed by 7914

Abstract

Photodynamic Therapy (PDT) has become one of the most promising treatment against autoimmune diseases, such as rheumatoid arthritis (RA), as well as in the treatment of different types of cancer, since it is a non-invasive method and easy to carry out. The three main ingredients of PDT are light irradiation, oxygen, and a photosensitizer (PS). Light irradiation depends on the type of molecule or compound to be used as a PS. The concentration of O₂ fluctuates according to the medium where the target tissue is located and over time, although it is known that it is possible to provide oxygenated species to the treated area through the PS itself. Finally, each PS has its own characteristics, the efficacy of which depends on multiple factors, such as solubility, administration technique, retention time, stability, excitation wavelength, biocompatibility, and clearance, among others. Therefore, it is essential to have a thorough knowledge of the disease to select the best PS for a specific target, such as RA. In this review we will present the PSs used in the last three decades to treat RA under PDT protocol, as well as insights on the relevant strategies. Full article

(This article belongs to the Special Issue Insights into Photodynamic Therapy)

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