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Photodynamic Therapy in Cancer Treatment
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Photodynamic Therapy in Cancer Treatment

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Photochemistry".

Deadline for manuscript submissions: closed (30 September 2020) | Viewed by 35874

Special Issue Editors

Dr. M. Amparo F. Faustino

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Guest Editor
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: porphyrin derivatives and analogues; cyclo-addition reactions; photodynamic applications; DSSC cells; antimicrobials; antitumoral
Special Issues, Collections and Topics in MDPI journals
Dr. Carlos Monteiro

E-Mail Website
Co-Guest Editor
LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: organic synthesis; fine chemistry; medicinal chemistry; pharmaceutical chemistry; drug development; porphyrin; photochemistry; photodynamic therapy; antimicrobial; ceramic materials; decarbonization; synthetic fuels
Special Issues, Collections and Topics in MDPI journals
Dr. Catarina I. V. Ramos

E-Mail Website
Co-Guest Editor
QOPNA & LAQV-REQUIMTE, Department of Chemistry, University of Aveiro, 3810-193 Aveiro, Portugal
Interests: drug development; water-soluble tetrapyrrolic macrocycles for biomedical applications; cationic and anionic derivatives; spectrophotometric methodologies; mass spectrometry; high-order DNA structures; G-quadruplex–porphyrinoid interactions; targeting telomeres and telomerase; telomerase inhibition; oncogenes; cancer cell proliferation control; photodynamic therapy in cancer
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a clinically approved treatment based on the administration of a photosensitizing molecule, its accumulation in the target tissue, and illumination with light, which is selectively absorbed by the photosensitizer (PS). In fact, the clinical approach of PDT through the combination of the photosensitizer, oxygen, and visible or near-infrared light irradiation leads to the production of cytotoxic reactive oxygen species (ROS), which trigger a cascade of reactions that lead to the destruction of tumor cells and tumor vasculature, making PDT an effective anticancer procedure. In comparison with traditional oncological therapies, PDT has several advantages; it is relatively non-invasive because irradiation is confined to the tumor site, and the photosensitizer accumulates predominantly in cancer cells, thus showing lower systemic toxicity and a relatively selective destruction of neoplastic cells. PDT also has a good tolerability profile, the absence of specific resistance mechanisms, a good cosmetic outcome, and the ability to stimulate the immune system. However, PDT has some limitations, and thus, there is a significant room for improvement, especially in the area of new and more efficient PS molecules. Better PS molecules should be rationally designed and prepared to match, as close as possible, the properties that define the profile of the ideal PS.

The aim of this Special Issue, Photodynamic Therapy in Cancer Treatment, is to provide the latest findings in this research field, namely, new photosensitizers, photochemical and photobiological aspects, targeting, and biological applications. We invite original research papers and comprehensive reviews covering any aspect related to the abovementioned topics.

Prof. Dr. M. Amparo F. Faustino
Dr. Carlos J. P. Monteiro
Dr. Catarina I. V. Ramos
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Molecules is an international peer-reviewed open access semimonthly 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 2700 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
  • Synthesis of new photosensitizers
  • Functionalization/bioconjugation of photosensitizers
  • Theranostics
  • Tumor imaging
  • Drug delivery
  • Antitumor immune response
  • Combination of PDT and chemotherapy
  • Photosensitizer targeting
  • Photochemical and photobiological aspects of PDT
  • Biological applications
  • Translational research

Published Papers (8 papers)

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Research

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10 pages, 1429 KiB  
Article
The Assessment of the Combined Treatment of 5-ALA Mediated Photodynamic Therapy and Thalidomide on 4T1 Breast Carcinoma and 2H11 Endothelial Cell Line
by Krzysztof Zduniak, Katarzyna Gdesz-Birula, Marta Woźniak, Kamila Duś-Szachniewicz and Piotr Ziółkowski
Molecules 2020, 25(21), 5184; https://doi.org/10.3390/molecules25215184 - 07 Nov 2020
Cited by 8 | Viewed by 2142
Abstract
Photodynamic therapy (PDT) is a low-invasive method of treatment of various diseases, mainly neoplastic conditions. PDT has been experimentally combined with multiple treatment methods. In this study, we tested a combination of 5-aminolevulinic acid (5-ALA) mediated PDT with thalidomide (TMD), which is a [...] Read more.
Photodynamic therapy (PDT) is a low-invasive method of treatment of various diseases, mainly neoplastic conditions. PDT has been experimentally combined with multiple treatment methods. In this study, we tested a combination of 5-aminolevulinic acid (5-ALA) mediated PDT with thalidomide (TMD), which is a drug presently used in the treatment of plasma cell myeloma. TMD and PDT share similar modes of action in neoplastic conditions. Using 4T1 murine breast carcinoma and 2H11 murine endothelial cells lines as an experimental tumor model, we tested 5-ALA-PDT and TMD combination in terms of cytotoxicity, apoptosis, Vascular Endothelial Growth Factor (VEGF) expression, and, in 2H11 cells, migration capabilities by wound healing assay. We have found an enhancement of cytotoxicity in 4T1 cells, whereas, in normal 2H11 cells, this effect was not statistically significant. The addition of TMD decreased the production of VEGF after PDT in 2H11 cell line. Our results reveal enhanced effectiveness of 5-ALA-PDT with TMD treatment compared to 5-ALA-PDT or TMD treatment alone. The addition of TMD may be a promising proceeding of the anti-tumor effect of PDT by decreasing the VEGF concentration in the culture medium. Further studies, including testing on different cell lines, are needed to confirm this assumption. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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18 pages, 2082 KiB  
Article
Synthesis and Photophysical Properties of Tumor-Targeted Water-Soluble BODIPY Photosensitizers for Photodynamic Therapy
by Duy Khuong Mai, Byungman Kang, Temmy Pegarro Vales, Isabel Wen Badon, Sung Cho, Joomin Lee, Eunae Kim and Ho-Joong Kim
Molecules 2020, 25(15), 3340; https://doi.org/10.3390/molecules25153340 - 23 Jul 2020
Cited by 19 | Viewed by 4182
Abstract
The synthesis of three water-soluble lactose-modified 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers with tumor-targeting capabilities is reported, including an investigation into their photodynamic therapeutic activity on three distinct cancer cell lines (human hepatoma Huh7, cervical cancer HeLa, and breast cancer MCF-7 cell lines). The halogenated BODIPY [...] Read more.
The synthesis of three water-soluble lactose-modified 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY)-based photosensitizers with tumor-targeting capabilities is reported, including an investigation into their photodynamic therapeutic activity on three distinct cancer cell lines (human hepatoma Huh7, cervical cancer HeLa, and breast cancer MCF-7 cell lines). The halogenated BODIPY dyes exhibited a decreased fluorescence quantum yield compared to their non-halogenated counterpart, and facilitated the efficient generation of singlet oxygen species. The synthesized dyes exhibited low cytotoxicities in the dark and high photodynamic therapeutic capabilities against the treated cancer cell lines following irradiation at 530 nm. Moreover, the incorporation of lactose moieties led to an enhanced cellular uptake of the BODIPY dyes. Collectively, the results presented herein provide promising insights for the development of photodynamic therapeutic agents for cancer treatment. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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15 pages, 1903 KiB  
Article
Influence of Polymer Charge on the Localization and Dark- and Photo-Induced Toxicity of a Potential Type I Photosensitizer in Cancer Cell Models
by Mikael Lindgren, Odrun A. Gederaas, Monica Siksjø, Tom A. Hansen, Lena Chen, Bastien Mettra, Chantal Andraud and Cyrille Monnereau
Molecules 2020, 25(5), 1127; https://doi.org/10.3390/molecules25051127 - 03 Mar 2020
Cited by 4 | Viewed by 3308
Abstract
A current trend within photo-dynamic therapy (PDT) is the development of molecular systems targeting hypoxic tumors. Thus, type I PDT sensitizers could here overcome traditional type II molecular systems that rely on the photo-initiated production of toxic singlet oxygen. Here, we investigate the [...] Read more.
A current trend within photo-dynamic therapy (PDT) is the development of molecular systems targeting hypoxic tumors. Thus, type I PDT sensitizers could here overcome traditional type II molecular systems that rely on the photo-initiated production of toxic singlet oxygen. Here, we investigate the cell localization properties and toxicity of two polymeric anthracene-based fluorescent probes (neutral Ant-PHEA and cationic Ant-PIm). The cell death and DNA damage of Chinese hamster ovary cancer cells (CHO-K1) were characterized as combining PDT, cell survival studies (MTT-assay), and comet assay. Confocal microscopy was utilized on samples incubated together with either DRAQ5, Lyso Tracker Red, or Mito Tracker Deep Red in order to map the localization of the sensitizer into the nucleus and other cell compartments. While Ant-PHEA did not cause significant damage to the cell, Ant-PIm showed increased cell death upon illumination, at the cost of a significant dark toxicity. Both anthracene chromophores localized in cell compartments of the cytosol. Ant-PIm showed a markedly improved selectivity toward lysosomes and mitochondria, two important biological compartments for the cell’s survival. None of the two anthracene chromophores showed singlet oxygen formation upon excitation in solvents such as deuterium oxide or methanol. Conclusively, the significant photo-induced cell death that could be observed with Ant-PIm suggests a possible type I PDT mechanism rather than the usual type II mechanism. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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Review

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12 pages, 669 KiB  
Review
Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies
by Lucas Nogueira, Andrew T. Tracey, Ricardo Alvim, Peter Reisz, Avigdor Scherz, Jonathan A. Coleman and Kwanghee Kim
Molecules 2020, 25(22), 5417; https://doi.org/10.3390/molecules25225417 - 19 Nov 2020
Cited by 12 | Viewed by 2418
Abstract
With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of [...] Read more.
With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies. Herein, we describe the evolution of photodynamic therapy in urologic oncology and the role of VTP in emerging treatment paradigms. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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27 pages, 1910 KiB  
Review
Photodynamic Therapy for Basal Cell Carcinoma: The Clinical Context for Future Research Priorities
by Nicholas J. Collier and Lesley E. Rhodes
Molecules 2020, 25(22), 5398; https://doi.org/10.3390/molecules25225398 - 18 Nov 2020
Cited by 26 | Viewed by 4135
Abstract
Photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC). BCC is the most common human cancer and also a convenient cancer in which to study PDT treatment. This review clarifies challenges to researchers evident from the clinical use [...] Read more.
Photodynamic therapy (PDT) is an established treatment option for low-risk basal cell carcinoma (BCC). BCC is the most common human cancer and also a convenient cancer in which to study PDT treatment. This review clarifies challenges to researchers evident from the clinical use of PDT in BCC treatment. It outlines the context of PDT and how PDT treatments for BCC have been developed hitherto. The sections examine the development of systemic and subsequently topical photosensitizers, light delivery regimens, and the use of PDT in different patient populations and subtypes of BCC. The outcomes of topical PDT are discussed in comparison with alternative treatments, and topical PDT applications in combination and adjuvant therapy are considered. The intention is to summarize the clinical relevance and expose areas of research need in the BCC context, ultimately to facilitate improvements in PDT treatment. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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54 pages, 1488 KiB  
Review
Ligand-Targeted Delivery of Photosensitizers for Cancer Treatment
by Piotr Gierlich, Ana I. Mata, Claire Donohoe, Rui M. M. Brito, Mathias O. Senge and Lígia C. Gomes-da-Silva
Molecules 2020, 25(22), 5317; https://doi.org/10.3390/molecules25225317 - 14 Nov 2020
Cited by 47 | Viewed by 6841
Abstract
Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity [...] Read more.
Photodynamic therapy (PDT) is a promising cancer treatment which involves a photosensitizer (PS), light at a specific wavelength for PS activation and oxygen, which combine to elicit cell death. While the illumination required to activate a PS imparts a certain amount of selectivity to PDT treatments, poor tumor accumulation and cell internalization are still inherent properties of most intravenously administered PSs. As a result, common consequences of PDT include skin photosensitivity. To overcome the mentioned issues, PSs may be tailored to specifically target overexpressed biomarkers of tumors. This active targeting can be achieved by direct conjugation of the PS to a ligand with enhanced affinity for a target overexpressed on cancer cells and/or other cells of the tumor microenvironment. Alternatively, PSs may be incorporated into ligand-targeted nanocarriers, which may also encompass multi-functionalities, including diagnosis and therapy. In this review, we highlight the major advances in active targeting of PSs, either by means of ligand-derived bioconjugates or by exploiting ligand-targeting nanocarriers. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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16 pages, 2972 KiB  
Review
Daylight Photodynamic Therapy: An Update
by Chaw-Ning Lee, Rosie Hsu, Hsuan Chen and Tak-Wah Wong
Molecules 2020, 25(21), 5195; https://doi.org/10.3390/molecules25215195 - 08 Nov 2020
Cited by 61 | Viewed by 6982
Abstract
Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be [...] Read more.
Daylight photodynamic therapy (dPDT) uses sunlight as a light source to treat superficial skin cancer. Using sunlight as a therapeutic device has been present for centuries, forming the basis of photodynamic therapy in the 20th century. Compared to conventional PDT, dPDT can be a less painful, more convenient and an effective alternative. The first clinical uses of dPDT on skin cancers began in Copenhagen in 2008. Currently, aminolevulinic acid-mediated dPDT has been approved to treat actinic keratosis patients in Europe. In this review article, we introduce the history and mechanism of dPDT and focus on the pros and cons of dPDT in treating superficial skin cancers. The future applications of dPDT on other skin diseases are expected to expand as conventional PDT evolves. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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39 pages, 9188 KiB  
Review
Corroles and Hexaphyrins: Synthesis and Application in Cancer Photodynamic Therapy
by Susana M. M. Lopes, Marta Pineiro and Teresa M. V. D. Pinho e Melo
Molecules 2020, 25(15), 3450; https://doi.org/10.3390/molecules25153450 - 29 Jul 2020
Cited by 29 | Viewed by 4596
Abstract
Corroles and hexaphyrins are porphyrinoids with great potential for diverse applications. Like porphyrins, many of their applications are based on their unique capability to interact with light, i.e., based on their photophysical properties. Corroles have intense absorptions in the low-energy region of the [...] Read more.
Corroles and hexaphyrins are porphyrinoids with great potential for diverse applications. Like porphyrins, many of their applications are based on their unique capability to interact with light, i.e., based on their photophysical properties. Corroles have intense absorptions in the low-energy region of the uv-vis, while hexaphyrins have the capability to absorb light in the near-infrared (NIR) region, presenting photophysical features which are complementary to those of porphyrins. Despite the increasing interest in corroles and hexaphyrins in recent years, the full potential of both classes of compounds, regarding biological applications, has been hampered by their challenging synthesis. Herein, recent developments in the synthesis of corroles and hexaphyrins are reviewed, highlighting their potential application in photodynamic therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer Treatment)
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