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Photodynamic Therapy for Cancers: Advances and Perspectives
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Photodynamic Therapy for Cancers: Advances and Perspectives

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Cell Proliferation and Division".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 10356

Special Issue Editors

Prof. Dr. Fabio Mammano

E-Mail Website1 Website2
Guest Editor
1. Department of Physics and Astronomy “G. Galilei”, University of Padova, 35131 Padova, Italy
2. CNR Institute of Biochemistry and Cell Biology, 00015 Monterotondo, Italy
Interests: connexins; Ca2+ signaling; photodynamic therapy for cancer
Special Issues, Collections and Topics in MDPI journals
Dr. Greta Varchi

E-Mail Website
Guest Editor
Institute for the Organic Synthesis and Photoreactivity, Italian National Research Council, 40129 Bologna, Italy
Interests: cancer treatment; nanomedicine; drug discovery; drug delivery; organic chemistry; targeted therapy
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a promising approach for cancer treatment because of the absence of systemic toxicity of the photosensitizer (PS) in the absence of light irradiation, the possibility to irradiate the tumor selectively, the opportunity of treating multiple lesions simultaneously, and the ability to retreat a tumor to improve the response. Genetically encoded PSs, unlike chemical PSs, can be modified using genetic engineering techniques and targeted to unique cellular compartments, even within a single cell. The cytotoxic moieties that are produced during PDT have been shown to destroy tumors by multifactorial mechanisms, including effects on the vasculature and immunogenic cell death (ICD), which is regarded as one of the most promising ways to achieve total tumor cell and metastasis elimination. The therapy outcome may be also greatly influenced by bystander effects. Phototherapy and immunoadjuvant therapy have been used in combination clinically, wherein induced immunogenic cell death and enhanced antigen presentation synergy induce a systemic antitumor immune response to control residual tumor cells at the treatment site and distant metastases. Such combination strategies underline the importance of clinical studies that investigate the effectiveness of multimodal therapy approaches that incorporate PDT.

A better understanding of the effectiveness of PDT in the clinic as well as the optimization of new PSs and multimodal treatments may expand the clinical applications and effectiveness of PDT. We invite all scientists working in the PDT field to participate in this Special Issue. Original research articles, reviews, or shorter perspective articles on all aspects highlighted above related to PDT for cancer are welcome.

Prof. Dr. Fabio Mammano
Dr. Greta Varchi
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. Cells 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

  • PDT—photodynamic therapy
  • tumor
  • chemical photosensitizer
  • genetically encoded photosensitizer
  • light delivery
  • combination (combined) therapy
  • photoimmunotherapy (PIT)
  • immunogenic cell death
  • bystander effects
  • clinical application

Published Papers (4 papers)

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Research

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15 pages, 2687 KiB  
Article
Fibroblast Activation Protein-Targeting Minibody-IRDye700DX for Ablation of the Cancer-Associated Fibroblast with Photodynamic Therapy
by Esther M. M. Smeets, Daphne N. Dorst, Gerben M. Franssen, Merijn S. van Essen, Cathelijne Frielink, Martijn W. J. Stommel, Marija Trajkovic-Arsic, Phyllis F. Cheung, Jens T. Siveke, Ian Wilson, Alessandro Mascioni, Erik H. J. G. Aarntzen and Sanne A. M. van Lith
Cells 2023, 12(10), 1420; https://doi.org/10.3390/cells12101420 - 18 May 2023
Cited by 2 | Viewed by 2318
Abstract
Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers [...] Read more.
Fibroblast activation protein (FAP), expressed on cancer-associated fibroblasts, is a target for diagnosis and therapy in multiple tumour types. Strategies to systemically deplete FAP-expressing cells show efficacy; however, these induce toxicities, as FAP-expressing cells are found in normal tissues. FAP-targeted photodynamic therapy offers a solution, as it acts only locally and upon activation. Here, a FAP-binding minibody was conjugated to the chelator diethylenetriaminepentaacetic acid (DTPA) and the photosensitizer IRDye700DX (DTPA-700DX-MB). DTPA-700DX-MB showed efficient binding to FAP-overexpressing 3T3 murine fibroblasts (3T3-FAP) and induced the protein’s dose-dependent cytotoxicity upon light exposure. Biodistribution of DTPA-700DX-MB in mice carrying either subcutaneous or orthotopic tumours of murine pancreatic ductal adenocarcinoma cells (PDAC299) showed maximal tumour uptake of 111In-labelled DTPA-700DX-MB at 24 h post injection. Co-injection with an excess DTPA-700DX-MB reduced uptake, and autoradiography correlated with FAP expression in the stromal tumour region. Finally, in vivo therapeutic efficacy was determined in two simultaneous subcutaneous PDAC299 tumours; only one was treated with 690 nm light. Upregulation of an apoptosis marker was only observed in the treated tumours. In conclusion, DTPA-700DX-MB binds to FAP-expressing cells and targets PDAC299 tumours in mice with good signal-to-background ratios. Furthermore, the induced apoptosis indicates the feasibility of targeted depletion of FAP-expressing cells with photodynamic therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy for Cancers: Advances and Perspectives)
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14 pages, 3476 KiB  
Article
Light-Enhanced Cytotoxicity of Doxorubicin by Photoactivation
by Giulia Greco, Luca Ulfo, Eleonora Turrini, Alessia Marconi, Paolo Emidio Costantini, Tainah Dorina Marforio, Edoardo Jun Mattioli, Matteo Di Giosia, Alberto Danielli, Carmela Fimognari and Matteo Calvaresi
Cells 2023, 12(3), 392; https://doi.org/10.3390/cells12030392 - 21 Jan 2023
Cited by 7 | Viewed by 2563
Abstract
The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its [...] Read more.
The combination of photodynamic therapy with chemotherapy (photochemotherapy, PCT) can lead to additive or synergistic antitumor effects. Usually, two different molecules, a photosensitizer (PS) and a chemotherapeutic drug are used in PCT. Doxorubicin is one of the most successful chemotherapy drugs. Despite its high efficacy, two factors limit its clinical use: severe side effects and the development of chemoresistance. Doxorubicin is a chromophore, able to absorb light in the visible range, making it a potential PS. Here, we exploited the intrinsic photosensitizing properties of doxorubicin to enhance its anticancer activity in leukemia, breast, and epidermoid carcinoma cells, upon irradiation. Light can selectively trigger the local generation of reactive oxygen species (ROS), following photophysical pathways. Doxorubicin showed a concentration-dependent ability to generate peroxides and singlet oxygen upon irradiation. The underlying mechanisms leading to the increase in its cytotoxic activity were intracellular ROS generation and the induction of necrotic cell death. The nuclear localization of doxorubicin represents an added value for its use as a PS. The use of doxorubicin in PCT, simultaneously acting as a chemotherapeutic agent and a PS, may allow (i) an increase in the anticancer effects of the drug, and (ii) a decrease in its dose, and thus, its dose-related adverse effects. Full article
(This article belongs to the Special Issue Photodynamic Therapy for Cancers: Advances and Perspectives)
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22 pages, 4747 KiB  
Article
In Vitro Cell Death Mechanisms Induced by Dicoma anomala Root Extract in Combination with ZnPcS4 Mediated-Photodynamic Therapy in A549 Lung Cancer Cells
by Alexander Chota, Blassan P. George and Heidi Abrahamse
Cells 2022, 11(20), 3288; https://doi.org/10.3390/cells11203288 - 19 Oct 2022
Cited by 9 | Viewed by 2427
Abstract
Globally, lung cancer has remained the leading cause of morbidity and mortality in men and women. To enhance photodynamic therapeutic effects in vitro, the present study was designed to reduce dose-dependence in photodynamic therapy (PDT) and evaluate the anticancer effects of Dicoma anomala [...] Read more.
Globally, lung cancer has remained the leading cause of morbidity and mortality in men and women. To enhance photodynamic therapeutic effects in vitro, the present study was designed to reduce dose-dependence in photodynamic therapy (PDT) and evaluate the anticancer effects of Dicoma anomala (D. anomala) root extracts (i.e., chloroform (Chl), ethyl acetate (EtOAc), and methanol (MeOH)) on A549 lung cancer cells. The most active extract of D. anomala (D.A) was used to establish the 50% inhibitory concentration (IC50), which was further used to evaluate the anticancer efficacy of D.A in combination with ZnPcS4-mediated PDT IC50. The study further evaluated cell death mechanisms by cell viability/ cytotoxicity (LIVE/DEADTM assay), flow cytometry (Annexin V-fluorescein isothiocyanate (FITC)-propidium iodide (PI) staining), immunofluorescence (p38, p53, Bax, and caspase 3 expressions), and fluorometric multiplex assay (caspase 8 and 9) 24 h post-treatment with IC50 concentrations of ZnPcS4-mediated PDT and D.A MeOH root extract. Morphological changes were accompanied by a dose-dependent increase in cytotoxicity, decrease in viability, and proliferation in all experimental models. Apoptosis is the highly favored cell death mechanism observed in combination therapy groups. Apoptotic activities were supported by an increase in the number of dead cells in the LIVE/DEADTM assay, and the upregulation of p38, p53, Bax, caspase 3, 8, and 9 apoptotic proteins. In vitro experiments confirmed the cytotoxic and antiproliferative effects of D.A root extracts in monotherapy and in combination with ZnPcS4-mediated PDT. Taken together, our findings demonstrated that D.A could be a promising therapeutic candidate worth exploring in different types of cancer. Full article
(This article belongs to the Special Issue Photodynamic Therapy for Cancers: Advances and Perspectives)
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Review

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18 pages, 2698 KiB  
Review
Enhanced Photodynamic Therapy: A Review of Combined Energy Sources
by José A. Rodrigues and José H. Correia
Cells 2022, 11(24), 3995; https://doi.org/10.3390/cells11243995 - 10 Dec 2022
Cited by 22 | Viewed by 2278
Abstract
Photodynamic therapy (PDT) has been used in recent years as a non-invasive treatment for cancer, due to the side effects of traditional treatments such as surgery, radiotherapy, and chemotherapy. This therapeutic technique requires a photosensitizer, light energy, and oxygen to produce reactive oxygen [...] Read more.
Photodynamic therapy (PDT) has been used in recent years as a non-invasive treatment for cancer, due to the side effects of traditional treatments such as surgery, radiotherapy, and chemotherapy. This therapeutic technique requires a photosensitizer, light energy, and oxygen to produce reactive oxygen species (ROS) which mediate cellular toxicity. PDT is a useful non-invasive therapy for cancer treatment, but it has some limitations that need to be overcome, such as low-light-penetration depths, non-targeting photosensitizers, and tumor hypoxia. This review focuses on the latest innovative strategies based on the synergistic use of other energy sources, such as non-visible radiation of the electromagnetic spectrum (microwaves, infrared, and X-rays), ultrasound, and electric/magnetic fields, to overcome PDT limitations and enhance the therapeutic effect of PDT. The main principles, mechanisms, and crucial elements of PDT are also addressed. Full article
(This article belongs to the Special Issue Photodynamic Therapy for Cancers: Advances and Perspectives)
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