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 July 2025 | Viewed by 1097

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Guest Editor
CNRS, LRGP, Laboratoire Réactions et Génie des Procédés, Université de Lorraine, 54600 Nancy, France
Interests: photodynamic therapy; cancer; photosensitizer; nanoparticles; targeting; fluorescence
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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

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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 (2 papers)

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Research

23 pages, 5623 KiB  
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
Viewed by 344
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 KiB  
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
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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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