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Pharmaceuticals
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Photodynamic Therapy: 3rd Edition
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Photodynamic Therapy: 3rd Edition

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmaceutical Technology".

Deadline for manuscript submissions: 25 June 2026 | Viewed by 9999

Special Issue Editor

Dr. Céline Frochot

E-Mail Website
Guest Editor
LRGP, Laboratoire Réactions et Génie des Procédés, UMR 7274 CNRS-Université de Lorraine, 1 Rue Grandville, 54000 Nancy, France
Interests: photodynamic therapy; cancer; photosensitizer; nanoparticles; targeting; fluorescence
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a light-based photochemistry process. The illumination of a photoactivatable molecule (also called photosensitizer) with visible or near infrared light produces reactive oxygen toxic species to destroy tumor cells. This treatment modality leads to highly targeted actions because reactive oxygen species are produced only where light is applied. Light is not harmful, nor is the photoactivable molecule. Only the combination of three elements (photosensitizer, oxygen, and light) is required to induce photo-oxidation reactions. PDT has proven to be a promising modality in many medical applications, including cutaneous conditions, infectious diseases, and various cancers at different stages.

The journal Pharmaceuticals invites both reviews and original articles shedding light on the challenges and opportunities of the development of innovative solutions for photodynamic therapy. Topics include selective photoactivatable molecules targeting receptors overexpressed into tumor membranes and/or on neovessels; molecules exhibiting red shifted absorption for better penetration of light into tissues; photobactericidal agents; theranostics; and photodiagnosis. Reviews and original articles dealing with PDT-associated immunotherapy, new radiation systems such as X-rays, or new devices allowing for better illumination and/or dosimetry are also welcome.

Dr. Céline Frochot
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 250 words) can be sent to the Editorial Office for assessment.

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. Pharmaceuticals is an international peer-reviewed open access monthly 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 2900 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
  • photosensitizers
  • nanoparticles
  • photo-diagnosis
  • targeting
  • antimicrobial
  • X-rays excitation
  • two photon and upconversion
  • immunomodulation
  • dosimetry
  • hypoxia

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Published Papers (7 papers)

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Research

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12 pages, 1108 KB  
Article
Antimicrobial Efficacy of Photodynamic Therapy as an Adjunct to Brix 3000 in Minimally Invasive Management of Carious Lesions in Primary Teeth
by Zornitsa Lazarova, Raina Gergova and Nadezhda Mitova
Pharmaceuticals 2026, 19(2), 310; https://doi.org/10.3390/ph19020310 - 12 Feb 2026
Viewed by 474
Abstract
Background/Objectives: In the context of minimally invasive dentistry, photodynamic therapy (PDT) is regarded as a biologically oriented method for controlling microbial activity during caries excavation. Brix 3000 is a modern material used in chemo-mechanical removal of carious lesions, enabling selective elimination of [...] Read more.
Background/Objectives: In the context of minimally invasive dentistry, photodynamic therapy (PDT) is regarded as a biologically oriented method for controlling microbial activity during caries excavation. Brix 3000 is a modern material used in chemo-mechanical removal of carious lesions, enabling selective elimination of infected dentin. The present study compares the antimicrobial effectiveness of Brix 3000 and adjunctive PDT performed with the FotoSan 630 Intro Kit. Methods: This study included 30 children aged 4–7 years with carious lesions on primary molars classified as ICDAS II code 06. The lesions were allocated into two groups: Group 1 (the control group), encompassing 15 lesions excavated using Brix 3000 only, and Group 2 (the experimental group), encompassing 15 lesions excavated with Brix 3000 followed by adjunctive PDT with the FotoSan 630 Intro Kit. A total of 75 microbiological samples were collected: 30 from infected dentin before excavation, 30 from partially infected dentin after Brix 3000, and 15 (experimental group only) after subsequent PDT. Results: The results revealed a wide diversity of cariogenic microorganisms in the infected dentin, with S. mutans being the most frequently isolated and present in the highest quantities. Using Brix 3000 reduced microbial diversity and quantity following excavation of partially infected dentin, although S. mutans persisted at lower levels. Conclusions: After the additional photodynamic disinfection, no microorganisms were isolated from the partially infected dentin. Adjunctive PDT provides localized, non-invasive antimicrobial disinfection and can be integrated into minimally invasive caries management in primary teeth. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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18 pages, 3829 KB  
Article
Assessment of Photodynamic Therapy Penetration Depth in a Synthetic Pig Brain Model: A Novel Approach to Simulate the Reach of PDT-Mediated Effects In Vitro
by Nicolas Bader, Annika Hajosch, Christian Peschmann, Kathrin Stucke-Straub, Christian Rainer Wirtz, Richard Eric Kast, Marc-Eric Halatsch, Felix Capanni and Georg Karpel-Massler
Pharmaceuticals 2025, 18(12), 1837; https://doi.org/10.3390/ph18121837 - 2 Dec 2025
Viewed by 703
Abstract
Background/Objectives: Recurrence of glioblastoma (GBM) mostly occurs in close vicinity to the resection cavity. Therefore, our group has previously designed an implant to locally apply repetitive photodynamic therapy to mitigate tumor recurrence. The penetration depths of different wavelengths in brain tissue were exhaustively [...] Read more.
Background/Objectives: Recurrence of glioblastoma (GBM) mostly occurs in close vicinity to the resection cavity. Therefore, our group has previously designed an implant to locally apply repetitive photodynamic therapy to mitigate tumor recurrence. The penetration depths of different wavelengths in brain tissue were exhaustively studied before. However, the PDT-induced biological effects of 5-ALA-based PDT against GBM cells at different depths have not been evaluated yet. Methods: Therefore, a synthetic brain substitute material of 1–10 mm thickness and with optical properties comparable to the white or gray matter of pig brain was developed. Tumor cell viability was assessed in spheroids from six GBM cell lines using disks of varying thickness prepared from pig brain substitute material to mimic in vivo radiation attenuation. Results: Using an artificial brain tissue optical model based on material science, we have established a relationship between the PDT-induced effect of our PDT implant and the distance of migrating GBM cells from the resection cavity wall. Conclusions: This model may be helpful to aid optimization of the irradiation doses and fractionation required to attain the maximal therapeutic effect by long-term PDT applications. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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12 pages, 840 KB  
Article
Long-Term Efficacy of 5-ALA Photodynamic Therapy in Oral Lichen Planus Patients
by Magdalena Sulewska, Marta Wróblewska, Patryk Wiśniewski, Ewa Duraj, Jagoda Tomaszuk, Aleksandra Pietruska and Małgorzata Pietruska
Pharmaceuticals 2025, 18(11), 1676; https://doi.org/10.3390/ph18111676 - 5 Nov 2025
Cited by 2 | Viewed by 1815
Abstract
Background: Oral lichen planus (OLP) is a chronic mucosal disease associated with a risk of malignant transformation. Although topical corticosteroids are the standard therapy, prolonged administration may result in local and systemic complications. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been proposed [...] Read more.
Background: Oral lichen planus (OLP) is a chronic mucosal disease associated with a risk of malignant transformation. Although topical corticosteroids are the standard therapy, prolonged administration may result in local and systemic complications. Photodynamic therapy (PDT) with 5-aminolevulinic acid (ALA) has been proposed as a less invasive and safer alternative. Methods: In this prospective study, 44 patients with histologically verified OLP underwent a protocol consisting of ten consecutive weekly PDT sessions, each comprising a single irradiation. A 5% ALA formulation was topically applied, followed by illumination with a 630 nm red light device. Clinical outcomes were evaluated at baseline, immediately after therapy, and at 12- and 48-month follow-ups. Changes in lesion surface, REU index, and pain intensity on a visual analog scale (VAS) were analyzed. Results: Significant improvements were noted, with progressive and sustained decreases in lesion extent, REU scores, and VAS values throughout the 4-year observation period. The therapeutic response was consistent across different mucosal sites (keratinized and non-keratinized). No treatment-related adverse reactions were recorded. Conclusions: Long-term follow-up indicates that ALA-mediated PDT is a safe and effective management option for both reticular and erosive variants of OLP. Its durable clinical benefits and favorable safety profile support its role as an alternative to corticosteroid therapy. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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22 pages, 5623 KB  
Article
Lanthanides-Based Nanoparticles Conjugated with Rose Bengal for FRET-Mediated X-Ray-Induced PDT
by Batoul Dhaini, Joël Daouk, Hervé Schohn, Philippe Arnoux, Valérie Jouan-Hureaux, Albert Moussaron, Agnès Hagege, Mathilde Achard, Samir Acherar, Tayssir Hamieh and Céline Frochot
Pharmaceuticals 2025, 18(5), 672; https://doi.org/10.3390/ph18050672 - 1 May 2025
Cited by 2 | Viewed by 1879
Abstract
In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of [...] Read more.
In order to find a good candidate for Förster Resonance Energy Transfer (FRET)-mediated X-ray-induced photodynamic therapy (X-PDT) for the treatment of cancer, lanthanide (Ln)-based AGuIX nanoparticles (NPs) conjugated with Rose Bengal (RB) as a photosensitizer (PS) were synthesized. X-PDT overcomes the problem of the poor penetration of visible light into tissues, which limits the efficacy of PDT in the treatment of deep-seated tumors. It is essential to optimize FRET efficiency by maximizing the overlap integral between donor emission and acceptor absorption and lengthening the duration of the donor emission. In this study, we optimized energy transfer between a scintillator (Sc) as a donor and a PS as an acceptor. Terbium (Tb) and Gadolinium (Gd) as Scs and Rose RB as a PS were chosen. The study of energy transfer between Tb, Gd and RB in solution and chelated on AGuIX NPs proved to be FRET-like. RB was conjugated directly onto AGuIX NPs (i.e., AGuIX Ln@RB), and the use of a spacer arm (i.e., AGuIX Ln@spacer arm-RB) increased FRET efficiency. Singlet oxygen production by these NPs was observed under UV–visible illumination and X-ray irradiation. The in vitro bioassay demonstrated 52% cell death of U-251MG derived from human malignant glioblastoma multiforme at a concentration of 1 μM RB after illumination and irradiation (2 Gy, 320 kV, 10 mA, 3 Gy/min at 47 cm). In addition, the RB-coupled NRP-1-targeting peptide (i.e., K(RB)DKPPR) was conjugated onto AGuIX NPs by a thiol-maleimide click chemistry reaction, and an affinity in the nM range was observed. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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28 pages, 6528 KB  
Article
Endoplasmic Reticulum-Targeted Phototherapy Remodels the Tumor Immunopeptidome to Enhance Immunogenic Cell Death and Adaptive Anti-Tumor Immunity
by Weidong Xiao, Mingquan Gao, Banghui Mo, Xie Huang, Zaizhi Du, Shufeng Wang, Jianhong Chen, Shenglin Luo and Haiyan Xing
Pharmaceuticals 2025, 18(4), 491; https://doi.org/10.3390/ph18040491 - 28 Mar 2025
Cited by 3 | Viewed by 2139
Abstract
Background: Endoplasmic reticulum (ER)-targeted phototherapy has emerged as a promising approach to amplify ER stress, induce immunogenic cell death (ICD), and enhance anti-tumor immunity. However, its impact on the antigenicity of dying tumor cells remains poorly understood. Methods: Laser activation of the ER-targeted [...] Read more.
Background: Endoplasmic reticulum (ER)-targeted phototherapy has emerged as a promising approach to amplify ER stress, induce immunogenic cell death (ICD), and enhance anti-tumor immunity. However, its impact on the antigenicity of dying tumor cells remains poorly understood. Methods: Laser activation of the ER-targeted photosensitizer ER-Cy-poNO2 was performed to investigate its effects on tumor cell antigenicity. Transcriptomic analysis was carried out to assess gene expression changes. Immunopeptidomics profiling was used to identify high-affinity major histocompatibility complex class I (MHC-I) ligands. In vitro functional studies were conducted to evaluate dendritic cell maturation and T lymphocyte activation, while in vivo experiments were performed by combining the identified peptide with poly IC to evaluate anti-tumor immunity. Results: Laser activation of ER-Cy-poNO2 significantly remodeled the antigenic landscape of 4T-1 tumor cells, enhancing their immunogenicity. Transcriptomic analysis revealed upregulation of antigen processing and presentation pathways. Immunopeptidomics profiling identified multiple high-affinity MHC-I ligands, with IF4G3986–994 (QGPKTIEQI) showing exceptional immunogenicity. In vitro, IF4G3986–994 promoted dendritic cell maturation and enhanced T lymphocytes activation. In vivo, the combination of IF4G3986–994 with poly IC elicited robust anti-tumor immunity, characterized by increased CD8+ T lymphocytes infiltration, reduced regulatory T cells (Tregs) in the tumor microenvironment, elevated systemic Interferon-gamma (IFN-γ) levels, and significant tumor growth inhibition without systemic toxicity. Conclusions: These findings establish a mechanistic link between ER stress-driven ICD, immunopeptidome remodeling, and adaptive immune activation, highlighting the potential of ER-targeted phototherapy as a platform for identifying immunogenic peptides and advancing peptide-based cancer vaccines. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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Review

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52 pages, 16801 KB  
Review
Delving into the Inception of BODIPY Dyes: Paradigms of In Vivo Bioimaging, Chemosensing, and Photodynamic/Photothermal Therapy
by Olivia Basant, Edgardo Lobo, Gyliann Peña and Maged Henary
Pharmaceuticals 2026, 19(1), 169; https://doi.org/10.3390/ph19010169 - 18 Jan 2026
Cited by 1 | Viewed by 1214
Abstract
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase [...] Read more.
Boron-dipyrromethene (BODIPY) dyes belong to a class of organoboron compounds that have become ubiquitous for researchers in areas of fluorescence imaging, photodynamic therapy, and optoelectronics. The intrinsic qualities of BODIPY dyes and their meso-modified structural analogs, Aza-BODIPY dyes, have propelled their recent increase in use in biomedical applications. The two scaffolds have high quantum yields, narrow absorption, and emission bandwidths with large Stokes’ shifts, and high photostability and thermal stability. Because their properties are independent of solvent polarity and dye functionality, they can be tuned to promote novel analytical methods, resulting in the adaptation of the physicochemical and spectral properties of the dyes. In this review of BODIPY and Aza-BODIPY scaffolds, we will summarize their spectral properties, synthetic methods of preparation, and applications reported between 2014 and 2025. This review aims to summarize the advances in chemosensing, especially pH sensor development, and the advances in NIR-II window bioimaging probes. We hope that this succinct overview of Aza-BODIPY scaffolds will highlight their untapped potential, elucidating insights that may catalyze novel ideas in the physical organic realm of BODIPY. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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19 pages, 642 KB  
Review
Photodynamic Action of Hypocrellin A and Hypocrellin B against Cancer—A Review
by Jinju Huang, Siu Kan Law, Albert Wing Nang Leung and Chuanshan Xu
Pharmaceuticals 2025, 18(12), 1847; https://doi.org/10.3390/ph18121847 - 3 Dec 2025
Cited by 1 | Viewed by 1054
Abstract
Cancer is a major global health concern, affecting nearly 20 million individuals annually, according to the International Agency for Research on Cancer (IARC). There are some unconventional and conventional treatments for cancer. Typically, they span a wide spectrum of conventional and advanced therapeutic [...] Read more.
Cancer is a major global health concern, affecting nearly 20 million individuals annually, according to the International Agency for Research on Cancer (IARC). There are some unconventional and conventional treatments for cancer. Typically, they span a wide spectrum of conventional and advanced therapeutic approaches, such as photodynamic therapy (PDT). This has long been valued for its non-invasive, targeted, and minimally toxic approach in the management of cancer. More importantly, PDT results in fewer operative and post-operative major complications, faster recovery times, reduced operating time, and saved costs. There are two types of photosensitizers in PDT, including synthetics (e.g., hematoporphyrin derivative, photofrin II, verteporfin) and natural (e.g., Hypocrellin A (HA) and Hypocrellin B (HB)). Nine electronic databases—WanFang Data, PubMed, ScienceDirect, Scopus, Web of Science, Springer Link, SciFinder, and the China National Knowledge Infrastructure (CNKI)—were systematically searched for this review, covering the literature published within the past 20 to 30 years (time range), without language restrictions. Studies were included if they were identified using the keywords Hypocrellin A, Hypocrellin B, photodynamic therapy, and cancer (inclusion criteria). All eligible papers were collected, critically analyzed, and summarized. Duplicate records were excluded during the screening process (exclusion criteria). HA and HB, derived from the fungus Hypocrella bambusae, offer a natural alternative with lower toxicity. However, these compounds are still in the in vitro or in vivo, and must meet rigorous standards for “quality”, “safety”, “efficacy”, “pharmacokinetics”, as well as “regulatory compliance” before entering clinical trials. “Curcumin” is a successful PS for traditional Chinese medicine used in PDT during clinical study and it is used as a benchmark for HB. Currently, scientists are paying attention to “nanotechnology” that enhances hypocrellin’s properties in PDT for achieving clinical goals, but further investigations are required. Full article
(This article belongs to the Special Issue Photodynamic Therapy: 3rd Edition)
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