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Biomedicines
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Photodynamic Therapy in Cancer
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Photodynamic Therapy in Cancer

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cancer Biology and Oncology".

Deadline for manuscript submissions: closed (30 June 2023) | Viewed by 18030

Special Issue Editor

Dr. Shazia Bano

E-Mail Website
Guest Editor
Laboratory of Dr. Tayyaba Hasan, Harvard Medical School, Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA
Interests: photodynamic therapy, tumor imaging-guided surgery; targeted drug delivery and nanomedicines; light and nanomaterial-based combination therapies

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is clinically approved for the treatment of various cancer and non-cancer applications. It exerts direct efficacy in destroying primary tumors, utilizing a light-activable molecule—termed a photosensitizer—light of an appropriate wavelength, along with oxygen, to impart cytotoxicity via the generation of reactive molecular species. In addition to therapeutic effects, photosensitizer-mediated fluorescence can also be used for image-guided surgery. Benefiting from the rapid development of nanotechnology, sophisticated targeting approaches and the emergence of nanocarriers for the codelivery of multiple therapeutics, PDT in combination with chemotherapy, photothermal therapy, radiotherapy, and immunotherapy can significantly enhance treatment outcomes, minimizing the off-target effects.

This Special Issue, Photodynamic Therapy of Cancer, aims to publish the latest research and translational work in the field of PDT in original articles related to nanodelivery carriers, photochemical and photobiological aspects, targeted drug delivery, tumor image-guided surgery, immunogenic cell death, and PDT-based multimodal therapies of cancer.

Dr. Shazia Bano
Guest Editor

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.

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 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
  • targeted drug delivery and drug release systems
  • photodiagnosis/tumor imaging
  • PDT-induced immunogenic cell death
  • nanomaterials-based combination therapies
  • theranostics

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Published Papers (6 papers)

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Research

11 pages, 2581 KiB  
Article
Induction of Skin Cancer by Long-Term Blue Light Irradiation
by Keiichi Hiramoto, Sayaka Kubo, Keiko Tsuji, Daijiro Sugiyama and Hideo Hamano
Biomedicines 2023, 11(8), 2321; https://doi.org/10.3390/biomedicines11082321 - 21 Aug 2023
Cited by 8 | Viewed by 4260
Abstract
Presently, people are not only exposed to sunlight but also to a large amount of blue light from personal computers and smartphones. This blue light has various effects on the living body. However, its effect on the induction of skin cancer is unknown. [...] Read more.
Presently, people are not only exposed to sunlight but also to a large amount of blue light from personal computers and smartphones. This blue light has various effects on the living body. However, its effect on the induction of skin cancer is unknown. In this study, we investigated the induction of skin cancer by long-term blue light irradiation. Hairless mice were irradiated with blue light (LED; peak emission 479 nm) every day for one year, and a control was irradiated with white light (LED), green light (LED; peak emission 538 nm), and red light (LED; peak emission 629 nm) for one year, respectively. Skin cancer was induced only in the mice exposed to blue light. Long-term blue light irradiation also increased the migration of neutrophils and macrophages involved in carcinogenesis in the skin. In neutrophils, an increased expression of citH3 and PAD4 was observed, suggesting the possibility of NETosis. Conversely, in macrophages, inflammatory macrophages (type 1 macrophages) increased and anti-inflammatory macrophages (type 2 macrophages) decreased due to continuous blue light irradiation. These findings suggest that long-term continuous irradiation with blue light induces neutrophil NETosis and an increase in type 1 macrophages, resulting in skin cancer. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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15 pages, 2479 KiB  
Article
A Robust Brain Tumor Detector Using BiLSTM and Mayfly Optimization and Multi-Level Thresholding
by Rabbia Mahum, Mohamed Sharaf, Haseeb Hassan, Lixin Liang and Bingding Huang
Biomedicines 2023, 11(6), 1715; https://doi.org/10.3390/biomedicines11061715 - 15 Jun 2023
Cited by 6 | Viewed by 1736
Abstract
A brain tumor refers to an abnormal growth of cells in the brain that can be either benign or malignant. Oncologists typically use various methods such as blood or visual tests to detect brain tumors, but these approaches can be time-consuming, require additional [...] Read more.
A brain tumor refers to an abnormal growth of cells in the brain that can be either benign or malignant. Oncologists typically use various methods such as blood or visual tests to detect brain tumors, but these approaches can be time-consuming, require additional human effort, and may not be effective in detecting small tumors. This work proposes an effective approach to brain tumor detection that combines segmentation and feature fusion. Segmentation is performed using the mayfly optimization algorithm with multilevel Kapur’s threshold technique to locate brain tumors in MRI scans. Key features are achieved from tumors employing Histogram of Oriented Gradients (HOG) and ResNet-V2, and a bidirectional long short-term memory (BiLSTM) network is used to classify tumors into three categories: pituitary, glioma, and meningioma. The suggested methodology is trained and tested on two datasets, Figshare and Harvard, achieving high accuracy, precision, recall, F1 score, and area under the curve (AUC). The results of a comparative analysis with existing DL and ML methods demonstrate that the proposed approach offers superior outcomes. This approach has the potential to improve brain tumor detection, particularly for small tumors, but further validation and testing are needed before clinical use. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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13 pages, 2047 KiB  
Article
5-Aminolevulinic Acid-Mediated Photodynamic Therapy Potentiates the Effectiveness of Doxorubicin in Ewing Sarcomas
by Lea Marocco, Felix Umrath, Saskia Sachsenmaier, Robert Rabiner, Nikolaus Wülker and Marina Danalache
Biomedicines 2022, 10(11), 2900; https://doi.org/10.3390/biomedicines10112900 - 11 Nov 2022
Cited by 2 | Viewed by 2040
Abstract
Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g., doxorubicin (DOX)), improving, thus, the anti-tumorigenic effects. In this study, we investigated the [...] Read more.
Ewing sarcomas (ES) are aggressive primary bone tumors that require radical therapy. Promising low toxicity, 5-aminolevulinic acid (5-ALA)-mediated photodynamic therapy (PDT) could enhance the effectiveness of conventional treatment modalities (e.g., doxorubicin (DOX)), improving, thus, the anti-tumorigenic effects. In this study, we investigated the effects of DOX and 5-ALA PDT alone or in combination on three different human ES cell lines. Cell viability, reactive oxygen species (ROS) production, and cellular stiffness were measured 24 h after PDT (blue light-wavelength 436 nm with 5-ALA) with or without DOX. ES cell lines have a different sensitivity to the same doses and exposure of 5-ALA PDT. DOX in combination with 5-ALA PDT was found to be effective in impairing the viability of all ES cells while also increasing cytotoxic activity by high ROS production. The stiffness of the ES cells increased significantly (p < 0.05) post treatment. Overall, our results showed that across multiple ES cell lines, 5-ALA PDT can successfully and safely be combined with DOX to potentiate the therapeutic effect. The 5-ALA PDT has the potential to be a highly effective treatment when used alone or in conjunction with other treatments. More research is needed to assess the effectiveness of 5-ALA PDT in in vivo settings. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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13 pages, 1494 KiB  
Article
Analysis of the Results of Severe Intraepithelial Squamous Cell Lesions and Preinvasive Cervical Cancer Phototheranostics in Women of Reproductive Age
by Aida Gilyadova, Anton Ishchenko, Anatoly Ishenko, Svetlana Samoilova, Artem Shiryaev, Alevtina Kiseleva, Natalya Petukhova, Kanamat Efendiev, Polina Alekseeva, Evgeny Stranadko, Victor Loschenov and Igor Reshetov
Biomedicines 2022, 10(10), 2521; https://doi.org/10.3390/biomedicines10102521 - 9 Oct 2022
Cited by 8 | Viewed by 3826
Abstract
(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients [...] Read more.
(1) Purpose: To investigate the efficacy and safety of using PDT in the treatment of severe intraepithelial squamous lesions of the cervix and preinvasive cervical cancer associated with HPV in women of reproductive age. (2) Methods: The examination and treatment of 45 patients aged 22–49 years with morphologically confirmed HPV-associated cervical intraepithelial neoplasia of a severe degree (17 patients) and preinvasive cervical cancer (28 patients) were performed. All patients underwent PDT of the cervix using a chlorin e6 photosensitizer; after which, the affected areas of the cervix were evaluated using video and spectral fluorescence diagnostics. PDT effectiveness was assessed on the basis of colposcopy data, a cytological examination of exo- and endocervix and PAP test scrapings or the liquid cytology method, and polymerase chain reaction for HPV carriage 4 weeks after PDT, as well as on the basis of histological and immunohistochemical studies of biopsy materials 5 weeks after PDT. The expression levels of the Ki-67 and p16 markers in the affected areas of the cervix were also assessed. (3) Results. All patients included in the study tolerated the intravenous administration of the photosensitizer well, with no side effects or allergic reactions observed. In 88.2% of patients with CIN III/HSIL and in 85.7% of women with preinvasive cervical cancer, the effect of the treatment was noted after the first PDT procedure, while complete regression of the dysplasia foci was observed in 15 women (88.2%) with CIN III/HSIL and in 25 patients (89.3%) with preinvasive cervical cancer. Partial regression to the form of LSIL/CIN I was noted in two cases (11.8%) in the CIN III/HSIL group and in three cases (10.7%) in the group of patients with preinvasive cervical cancer. After PDT, a statistically significant decrease in the expression of the Ki-67 and p16 levels relative to the initial values was noted. (4) Conclusions. The results obtained indicate the high efficiency of PDT with intravenous administration of the chlorin photosensitizer for the treatment of intraepithelial lesions of the cervix with a selective effect on pathologically altered tissue. The use of this approach makes it possible to preserve the normal anatomical and functional characteristics of the cervix, which is especially important for maintaining the fertility of patients. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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20 pages, 8157 KiB  
Article
Spheroidal Model of SKBR3 and U87MG Cancer Cells for Live Imaging of Caspase-3 during Apoptosis Induced by Singlet Oxygen in Photodynamic Therapy
by Viktória Pevná, Mariana Máčajová, Andrej Hovan, Gregor Bánó, Majlinda Meta, Boris Bilčík, Júlia Palková and Veronika Huntošová
Biomedicines 2022, 10(9), 2141; https://doi.org/10.3390/biomedicines10092141 - 31 Aug 2022
Cited by 7 | Viewed by 2772
Abstract
Aspects related to the response of cells to photodynamic therapy (PDT) have been well studied in cell cultures, which often grow in monolayers. In this work, we propose a spheroidal model of U87MG and SKBR3 cells designed to mimic superficial tumor tissue, small [...] Read more.
Aspects related to the response of cells to photodynamic therapy (PDT) have been well studied in cell cultures, which often grow in monolayers. In this work, we propose a spheroidal model of U87MG and SKBR3 cells designed to mimic superficial tumor tissue, small spheroids (<500 µm) suitable for confocal fluorescence microscopy, and larger spheroids (>500 µm) that can be xenografted onto quail chorioallantoic membrane (CAM) to study the effects of PDT in real time. Hypericin was used as a model molecule for a hydrophobic photosensitizer that can produce singlet oxygen (1O2). 1O2 production by hypericin was detected in SKBR3 and U87MG spheroid models using a label-free technique. Vital fluorescence microscopy and flow cytometry revealed the heterogeneity of caspase-3 distribution in the cells of the spheroids. The levels of caspase-3 and apoptosis increased in the cells of spheroids 24 h after PDT. Lactate dehydrogenase activity was evaluated in the spheroids as the most reliable assay to detect differences in phototoxicity. Finally, we demonstrated the applicability of U87MG spheroids on CAM in photodiagnostics. Overall, the variability and applicability of the prepared spheroid models were demonstrated in the PDT study. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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Graphical abstract

19 pages, 3731 KiB  
Article
Radiodynamic Therapy with Acridine Orange Is an Effective Treatment for Bone Metastases
by Gemma Di Pompo, Katsuyuki Kusuzaki, Marco Ponzetti, Vito Ferdinando Leone, Nicola Baldini and Sofia Avnet
Biomedicines 2022, 10(8), 1904; https://doi.org/10.3390/biomedicines10081904 - 5 Aug 2022
Cited by 4 | Viewed by 2355
Abstract
Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can [...] Read more.
Current multimodal treatment of bone metastases is partially effective and often associated with side effects, and novel therapeutic options are needed. Acridine orange is a photosensitizing molecule that accumulates in acidic compartments. After photo- or radiodynamic activation (AO-PDT or AO-RDT), acridine orange can induce lysosomal-mediated cell death, and we explored AO-RDT as an acid-targeted anticancer therapy for bone metastases. We used osteotropic carcinoma cells and human osteoclasts to assess the extracellular acidification and invasiveness of cancer cells, acridine orange uptake and lysosomal pH/stability, and the AO-RDT cytotoxicity in vitro. We then used a xenograft model of bone metastasis to compare AO-RDT to another antiacid therapeutic strategy (omeprazole). Carcinoma cells showed extracellular acidification activity and tumor-derived acidosis enhanced cancer invasiveness. Furthermore, cancer cells accumulated acridine orange more than osteoclasts and were more sensitive to lysosomal death. In vivo, omeprazole did not reduce osteolysis, whereas AO-RDT promoted cancer cell necrosis and inhibited tumor-induced bone resorption, without affecting osteoclasts. In conclusion, AO-RDT was selectively toxic only for carcinoma cells and effective to impair both tumor expansion in bone and tumor-associated osteolysis. We therefore suggest the use of AO-RDT, in combination with the standard antiresorptive therapies, to reduce disease burden in bone metastasis. Full article
(This article belongs to the Special Issue Photodynamic Therapy in Cancer)
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