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Photodynamic Therapy and Targeted PDT for Cancer Treatment

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Oncology".

Deadline for manuscript submissions: closed (15 February 2024) | Viewed by 6905

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Special Issue Editor

Prof. Dr. Nadira Delhem

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Guest Editor

CHU Lille, UMR 1189—OncoThAI (Thérapies Assistées par Lasers et Immunothérapies pour l’Oncologie), Université de Lille, Inserm, F-59000 Lille, France
Interests: photodynamic therapy, specific photosensitizer of third generation, PDT medical devices, immunomodulation (regulatory T cells, tolerogenic dendritic cells); immunotherapy; extracellular vesicles
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Special Issue Information

Dear Colleagues,

The main conventional strategies used in the treatment of cancers are surgery, radiotherapy, chemotherapy, targeted therapies, hormone therapy, and, more recently, with the success that we know of, immunotherapies. There is an obvious interest in combining new treatments most often targeting different cellular and molecular mechanisms. Unfortunately, many cancers remain resistant to both conventional treatments and combinations of these treatments. In this context, photodynamic therapy (PDT) appears as a relevant and innovative therapeutic alternative in oncology which could allow the optimal care of patients suffering from cancer who cannot benefit from the latest therapeutic advances or who are resistant to these treatments. The main advantage of PDT is the specificity regarding the direct destruction of tumor tissues while healthy tissues remain intact. Thus, PDT is already routinely used in some medical fields like onco-dermatology or onco-urology. However, even if PDT could have interesting potential in cancer applications, its efficacy remains today to be well demonstrated.

This Special Issue aims to highlight the potential of photodynamic therapy in the field of oncology, in cancers in general, rare cancers and cancers in therapeutic impasse with poor overall survival.

This Special Issue will present a particular focus on PDT using 1st and 2nd generation photosensitizers and more particularly third generation PS allowing the deployment of targeted PDT. The different PDT approaches may be presented by cellular, molecular and mechanistic study approaches (i) in vitro, passing from 2D cell cultures to 3D cultures using celluloids, spheroids or organoids; (ii) ex vivo studies on primary patient cells; (iii) in vivo with syngeneic or humanized murine preclinical models and finally (iv) pilot studies on patients or clinical trials whether or not combined with biological ancillary studies.

This Special Issue will also make it possible to highlight the specific targeting of new therapeutic markers in cancers by (i) biological and an immunological approachs including immunomodulation process (immunoactivation, immunoregulation, extracellular microvesicules, etc.); (ii) chemical approachs (synthesis of PS coupled with peptides, antibodies, small agonist or antagonist molecules, etc.); (iii) physical approachs (determination of optimal illumination parameters, optical simulations, etc.) and (iii) mechanical approachs, in particular by proposing new medical devices to ensure extracorporeal, intracavitary, interstitial PDT, etc.

Prof. Dr. Nadira Delhem
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.

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.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. 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
photosensitizer
organoids
spheroids, immune cells
pre-clinical and clinical models
immunomodulation
extracellular vesicules
illumination
chemical molecules
medical devices

Published Papers (4 papers)

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Research

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20 pages, 4582 KiB

Open AccessArticle

Single-Cell RNA Sequencing Reveals Immuno-Oncology Characteristics of Tumor-Infiltrating T Lymphocytes in Photodynamic Therapy-Treated Colorectal Cancer Mouse Model

by Eun-Ji Lee, Jang-Gi Choi, Jung Ho Han, Yong-Wan Kim, Junmo Lim and Hwan-Suck Chung

Int. J. Mol. Sci. 2023, 24(18), 13913; https://doi.org/10.3390/ijms241813913 - 10 Sep 2023

Cited by 1 | Viewed by 2132

Abstract

Photodynamic therapy (PDT) has shown promise in reducing metastatic colorectal cancer (CRC); however, the underlying mechanisms remain unclear. Modulating tumor-infiltrating immune cells by PDT may be achieved, which requires the characterization of immune cell populations in the tumor microenvironment by single-cell RNA sequencing (scRNA-seq). Here, we determined the effect of Chlorin e6 (Ce6)-mediated PDT on tumor-infiltrating T cells using scRNA-seq analysis. We used a humanized programmed death-1/programmed death ligand 1 (PD-1/PD-L1) MC38 cell allograft mouse model, considering its potential as an immunogenic cancer model and in combination with PD-1/PD-L1 immune checkpoint blockade. PDT treatment significantly reduced tumor growth in mice containing hPD-1/PD-L1 MC38 tumors. scRNA-seq analysis revealed that the PDT group had increased levels of CD8⁺ activated T cells and CD8⁺ cytotoxic T cells, but decreased levels of exhausted CD8⁺ T cells. PDT treatment also enhanced the infiltration of CD8⁺ T cells into tumors and increased the production of key effector molecules, including granzyme B and perforin 1. These findings provide insight into immune-therapeutic modulation for CRC patients and highlight the potential of PDT in overcoming immune evasion and enhancing antitumor immunity. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Targeted PDT for Cancer Treatment)

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Graphical abstract

20 pages, 3685 KiB

Open AccessArticle

Folate Receptor Targeted Photodynamic Therapy: A Novel Way to Stimulate Anti-Tumor Immune Response in Intraperitoneal Ovarian Cancer

by Martha Baydoun, Léa Boidin, Bertrand Leroux, Anne-Sophie Vignion-Dewalle, Alexandre Quilbe, Guillaume Paul Grolez, Henri Azaïs, Céline Frochot, Olivier Moralès and Nadira Delhem

Int. J. Mol. Sci. 2023, 24(14), 11288; https://doi.org/10.3390/ijms241411288 - 10 Jul 2023

Cited by 1 | Viewed by 1289

Abstract

Photodynamic therapy (PDT) has shown improvements in cancer treatment and in the induction of a proper anti-tumor immune response. However, current photosensitizers (PS) lack tumor specificity, resulting in reduced efficacy and side effects in patients with intraperitoneal ovarian cancer (OC). In order to target peritoneal metastases of OC, which overexpress folate receptor (FRα) in 80% of cases, we proposed a targeted PDT using a PS coupled with folic acid. Herein, we applied this targeted PDT in an in vivo mouse model of peritoneal ovarian carcinomatosis. The efficacy of the treatment was evaluated in mice without and with human peripheral blood mononuclear cell (PBMC) reconstitution. When mice were reconstituted, using a fractionized PDT protocol led to a significantly higher decrease in the tumor growth than that obtained in the non-reconstituted mice (p = 0.0469). Simultaneously, an immune response was reflected by an increase in NK cells, and both CD4+ and CD8+ T cells were activated. A promotion in cytokines IFNγ and TNFα and an inhibition in cytokines TGFβ, IL-8, and IL-10 was also noticed. Our work showed that a fractionized FRα-targeted PDT protocol is effective for the treatment of OC and goes beyond local induction of tumor cell death, with the promotion of a subsequent anti-tumor response. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Targeted PDT for Cancer Treatment)

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24 pages, 5861 KiB

Open AccessArticle

An Efficient 5-Aminolevulinic Acid Photodynamic Therapy Treatment for Human Hepatocellular Carcinoma

by Abhishek Kumar, Florian Pecquenard, Martha Baydoun, Alexandre Quilbé, Olivier Moralès, Bertrand Leroux, Lynda Aoudjehane, Filomena Conti, Emmanuel Boleslawski and Nadira Delhem

Int. J. Mol. Sci. 2023, 24(13), 10426; https://doi.org/10.3390/ijms241310426 - 21 Jun 2023

Viewed by 1609

Abstract

Photodynamic therapy (PDT) is a two-stage treatment relying on cytotoxicity induced by photoexcitation of a nontoxic dye, called photosensitizer (PS). Using 5-aminolevulinic acid (5-ALA), the pro-drug of PS protoporphyrin IX, we investigated the impact of PDT on hepatocellular carcinoma (HCC). Optimal 5-ALA PDT dose was determined on three HCC cell lines by analyzing cell death after treatment with varying doses. HCC-patient-derived tumor hepatocytes and healthy donor liver myofibroblasts were treated with optimal 5-ALA PDT doses. The proliferation of cancer cells and healthy donor immune cells cultured with 5-ALA-PDT-treated conditioned media was analyzed. Finally, therapy efficacy on humanized SCID mice model of HCC was investigated. 5-ALA PDT induced a dose-dependent decrease in viability, with an up-to-four-fold reduction in viability of patient tumor hepatocytes. The 5-ALA PDT treated conditioned media induced immune cell clonal expansion. 5-ALA PDT has no impact on myofibroblasts in terms of viability, while their activation decreased cancer cell proliferation and reduced the tumor growth rate of the in vivo model. For the first time, 5-ALA PDT has been validated on primary patient tumor hepatocytes and donor healthy liver myofibroblasts. 5-ALA PDT may be an effective anti-HCC therapy, which might induce an anti-tumor immune response. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Targeted PDT for Cancer Treatment)

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Review

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16 pages, 1400 KiB

Open AccessReview

The Use of Photodynamic Therapy for Head, Neck, and Brain Diseases

by Wojciech Domka, Dorota Bartusik-Aebisher, Wiktoria Mytych, Klaudia Dynarowicz and David Aebisher

Int. J. Mol. Sci. 2023, 24(14), 11867; https://doi.org/10.3390/ijms241411867 - 24 Jul 2023

Cited by 2 | Viewed by 1431

Abstract

Head–neck cancers as a group have the 7th highest rate of incidence worldwide. The most often diagnosed disease of the head and neck is squamous cell carcinoma (90% of cases). Another specific group of tumors is brain tumors. These can be divided into primary tumors and secondary tumors associated with metastasis. Research shows that treating head and neck cancers continues to be problematic and challenging, and researchers are actively seeking new treatments that would improve survival rates and reduce side effects. Irradiation of tumor tissue with the optimal wavelength of light in photodynamic therapy (PDT) generates predominantly singlet oxygen in tissue-based photosensitizers (PSs) or reactive oxygen radicals in the case of vascular PSs leading to cellular apoptosis and necrosis. A very important feature of PDT is that cells cannot become immune to the effects of singlet oxygen or reactive oxygen radicals. However, photosensitizer (PS) transport is influenced by the specific structures of cancer tumors and the concentration of PS decreases in cells far from the vessel lumen. Therefore, PSs may not reach tumor interiors, which decreases therapy effectiveness. The use of drug carriers and 3rd generation PSs that contain biocompatible functional groups makes it possible to control transport. This review of the current literature on PDT was conducted through databases such as PubMed and Scopus. The types of publications considered included clinical studies and most of the articles included were published in English. Based on the publications collected, we conclude that researchers have demonstrated the potential of PDT as a therapeutic platform for head, neck, and brain diseases. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Targeted PDT for Cancer Treatment)

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