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Photodynamic Therapy and Photodetection, 2nd Edition

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 August 2025 | Viewed by 10308

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Special Issue Editor

Dr. Petras Juzenas

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Guest Editor

Department of Pathology, Norwegian Radium Hospital, Oslo University Hospital, 0310 Oslo, Norway
Interests: biophotonics; photodynamic therapy (PDT); photodetection (PD); photosensitiser; photochemical internalization (PCI)

Special Issue Information

Dear Colleagues,

Photodynamic therapy (PDT) is a combination of light with a lesion-localising photosensitiser and oxygen present in the lesion leading to photochemical and photobiological reactions that result in irreversible photodamage to the lesion. Photodetection (PD) is based on fluorescence spectroscopic and imaging techniques that aim to demarcate a lesion from surrounding healthy tissues. The specific fluorescence in the lesion is induced by a light source with a suitable wavelength(s), with the prior administration of a photosensitiser or its precursor in most cases. Although the phenomena of PDT and PD were discovered more than 100 years ago, the results from preclinical and clinical studies conducted worldwide during the past >45 years have established modern PDT and PD as the clinical modalities for a number of malignant and non-malignant disorders. Photochemical internalization, a novel PDT-based technology, is employed for the efficient delivery of endosome-trapped molecules into the cytosol of cells. Targeted PDT and nanotechnology have recently been contributing to the development of PDT and PD. As yet, no universal mechanism of action by which PDT works has been described, and it may have different mechanisms depending on the type of lesion treated, photosensitiser employed and/or light dose applied. This Special Issue aims to provide an update regarding the current status of PDT and PD, with an emphasis on the mechanism of molecular action involved.

Dr. Petras Juzenas
Guest Editor

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Keywords

photodynamic therapy (PDT)
photodetection (PD)
photosensitiser
photochemical internalization (PCI)
quantum dots
nanoparticles
nanotechnology
targeted therapy
immunotherapy
vaccines

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Published Papers (9 papers)

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Research

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10 pages, 2344 KiB

Open AccessArticle

Fluence Rate-Dependent Kinetics of Light-Triggered Liposomal Doxorubicin Assessed by Quantitative Fluorescence-Based Endoscopic Probe

by Daniel J. Rohrbach, Kevin A. Carter, Dandan Luo, Shuai Shao, Semra Aygun-Sunar, Jonathan F. Lovell and Ulas Sunar

Int. J. Mol. Sci. 2025, 26(3), 1212; https://doi.org/10.3390/ijms26031212 - 30 Jan 2025

Viewed by 625

Abstract

Liposomal doxorubicin (Dox), a treatment option for recurrent ovarian cancer, often suffers from suboptimal biodistribution and efficacy, which might be addressed with precision drug delivery systems. Here, we introduce a catheter-based endoscopic probe designed for multispectral, quantitative monitoring of light-triggered drug release. This tool utilizes red-light photosensitive porphyrin−phospholipid (PoP), which is encapsulated in liposome bilayers to enhance targeted drug delivery. By integrating diffuse reflectance and fluorescence spectroscopy, our approach not only corrects for the effects of tissue optical properties but also ensures accurate drug delivery to deep-seated tumors. Preliminary results validate the probe’s effectiveness in controlled settings, highlighting its potential for future clinical adaptation. This study sets the stage for in vivo applications, enabling the exploration of next-generation treatment paradigms for the management of cancer that involve optimizing chemotherapy administration for precision and control. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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19 pages, 3180 KiB

Open AccessArticle

One Change, Many Benefits: A Glycine-Modified Bacteriochlorin with NIR Absorption and a Type I Photochemical Mechanism for Versatile Photodynamic Therapy

by Mateusz Werłos, Agata Barzowska-Gogola, Barbara Pucelik, Paweł Repetowski, Marta Warszyńska and Janusz M. Dąbrowski

Int. J. Mol. Sci. 2024, 25(23), 13132; https://doi.org/10.3390/ijms252313132 - 6 Dec 2024

Viewed by 945

Abstract

Difluorinated sulfonamide porphyrin (F₂PGly) and bacteriochlorin (F₂BGly), modified by glycine residues, were synthesized and evaluated for photodynamic therapy (PDT). F₂PGly exhibits superior stability and singlet oxygen generation efficiency but features a low-intensity band in the red range (λ_max = 639 nm). In contrast, F₂BGly shows a favorable, red-shifted absorption spectrum (λ_max = 746 nm) that aligns well with phototherapeutic window, facilitating deeper tissue penetration. Moreover, it demonstrates reasonable photostability, necessary for the efficient generation of both singlet oxygen (type II) and oxygen-centered radicals (type I mechanism) which contributes to enhanced therapeutic efficacy. Importantly, the glycine modifications in F₂BGly enhance its uptake in MCF-7 cells, known for their resistance to PDT due to efflux transport proteins like LAT1, showing great potential in the cancer cell-targeted PDT. The glycine groups potentially enable F₂BGly to bypass these barriers, resulting in increased intracellular accumulation and more effective Reactive Oxygen Species (ROS) generation under illumination. In vivo studies indicated promising vascular-targeted PDT results, with real-time fluorescence imaging used to monitor photosensitizer distribution prior to irradiation. These findings suggest that F₂BGly is a promising photosensitizer candidate with enhanced cancer cell selectivity and photodynamic efficiency, meriting further exploration in targeted PDT applications for multiple types of cancers. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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18 pages, 4346 KiB

Open AccessArticle

Reactive Oxygen Species-Sensitive Nanophotosensitizers Composed of Buthionine Sulfoximine-Conjugated Chitosan Oligosaccharide for Enhanced Photodynamic Treatment of Cancer Cells

by Hyo Young Lee, Ji-Sun Park, Taeyu Grace Kim, Taeyeon Kim, Do Hoon Kim, Jejung Yun and Young-IL Jeong

Int. J. Mol. Sci. 2024, 25(23), 12609; https://doi.org/10.3390/ijms252312609 - 24 Nov 2024

Viewed by 1095

Abstract

The efficacy of photodynamic therapy (PDT) based on traditional photosensitizers is generally limited by the cellular redox homeostasis system due to the reactive oxygen species (ROS) scavenging effect of glutathione (GSH). In this study, buthionine sulfoximine (BSO), a GSH inhibitor, was conjugated with the amine group of chitosan oligosaccharide (COS) using a thioketal linker (COSthBSO) to liberate BSO and chlorine e6 (Ce6) under oxidative stress, and then, Ce6-COSthBSO NP (Ce6-COSthBSO NP), fabricated by a dialysis procedure, showed an accelerated release rate of BSO and Ce6 by the addition of hydrogen peroxide, indicating that nanophotosensitizers have ROS sensitivity. In the in vitro cell culture study using HCT116 colon carcinoma cells, a combination of BSO and Ce6 efficiently suppressed the intracellular GSH and increased ROS production compared to the sole treatment of Ce6. In particular, Ce6-COSthBSO NP showed higher efficacy in the suppression of GSH levels and ROS production compared to the free Ce6 and Ce6/BSO combination. These results were due to the fact that Ce6-COSthBSO NP was efficiently delivered to the intracellular region, suppressed intracellular GSH levels, and elevated ROS levels. The in vivo animal tumor xenograft study demonstrated Ce6-COSthBSO NP being efficiently delivered to the tumor tissue, i.e., the fluorescence intensity in the tumor tissue was higher than those of other organs. The combination of Ce6 and BSO efficiently suppressed tumor growth compared to the sole treatment of Ce6, indicating that BSO might efficiently suppress GSH levels and increase ROS levels in the tumor microenvironment. Specifically, Ce6-COSthBSO NP showed the strongest performance in inhibition of tumor growth than those of Ce6 or the CE6/BSO combination, indicating that they were efficiently delivered to tumor tissue, increased ROS levels, and then efficiently inhibited tumor growth. We suggest that COSthBSO nanophotosensitizers are promising candidates for PDT treatment of cancer cells. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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16 pages, 2654 KiB

Open AccessArticle

Effects of Zinc Phthalocyanine Photodynamic Therapy on Vital Structures and Processes in Hela Cells

by Jakub Hosik, Barbora Hosikova, Svatopluk Binder, Rene Lenobel, Marketa Kolarikova, Lukas Malina, Hanna Dilenko, Katerina Langova, Robert Bajgar and Hana Kolarova

Int. J. Mol. Sci. 2024, 25(19), 10650; https://doi.org/10.3390/ijms251910650 - 3 Oct 2024

Viewed by 1252

Abstract

This work presents results on the efficiency of newly designed zinc phthalocyanine-mediated photodynamic therapy of both tumoral and nontumoral cell models using the MTT assay. Further detailed examinations of mechanistic and cell biological effects were focused on the HELA cervical cancer cell model. Here, ROS production, changes in the mitochondrial membrane potential, the determination of genotoxicity, and protein changes determined by capillary chromatography and tandem mass spectrometry with ESI were analyzed. The results showed that, in vitro, 5 Jcm⁻² ZnPc PDT caused a significant increase in reactive oxygen species. Still, except for superoxide dismutase, the levels of proteins involved in cell response to oxidative stress did not increase significantly. Furthermore, this therapy damaged mitochondrial membranes, which was proven by a more than 70% voltage-dependent channel protein 1 level decrease and by a 65% mitochondrial membrane potential change 24 h post-therapy. DNA impairment was assessed by an increased level of DNA fragmentation, which might be related to the decreased level of DDB1 (decrease in levels of more than 20% 24 h post-therapy), a protein responsible for maintaining genomic integrity and triggering the DNA repair pathways. Considering these results and the low effective concentration (LC50 = 30 nM), the therapy used is a potentially very promising antitumoral treatment. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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17 pages, 10876 KiB

Open AccessArticle

Shedding Light on Photodynamic Therapy in the Treatment of Necrobiosis Lipoidica: A Multicenter Real-Life Experience

by Federica Li Pomi, Alfonso Motolese, Alessia Paganelli, Mario Vaccaro, Alberico Motolese and Francesco Borgia

Int. J. Mol. Sci. 2024, 25(7), 3608; https://doi.org/10.3390/ijms25073608 - 23 Mar 2024

Cited by 2 | Viewed by 1784

Abstract

Necrobiosis Lipoidica (NL) is a dermatological condition characterized by the development of granulomatous inflammation leading to the degeneration of collagen and subsequent formation of yellowish-brown telangiectatic plaques usually localized on the pretibial skin of middle-aged females. Due to its rarity and unclear etiopathogenesis, therapeutic options for NL are not well-standardized. Among them, photodynamic therapy (PDT) is an emerging tool, although its efficacy has primarily been evaluated in single case reports or small case series. This study reports the real-life experience of a cohort of NL patients treated with PDT at the Section of Dermatology of the University Hospital of Messina and Reggio-Emilia. From 2013 to 2023, 17 patients were enrolled —5 males (29%) and 12 females (71%) aged between 16 and 56 years (mean age: 42 ± 13 years), with a median duration of NL of 8 years. The overall complete clearance (>75% lesion reduction) was 29%, while the partial clearance (25–75% lesion reduction) was 59%, with 12% being non-responders. This study adds to the little amount of evidence present in the literature regarding the effectiveness of PDT in the treatment of NL. Variability in treatment responses among patients underscores the need for personalized protocols, optimizing photosensitizers, light sources, and dosimetry. The standardization of treatment protocols and consensus guidelines are essential to ensure reproducibility and comparability across studies. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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9 pages, 1080 KiB

Open AccessCommunication

Carbon–TiO₂ Hybrid Quantum Dots for Photocatalytic Inactivation of Gram-Positive and Gram-Negative Bacteria

by Xiuli Dong, Yamin Liu, Audrey F. Adcock, Kirkland Sheriff, Weixiong Liang, Liju Yang and Ya-Ping Sun

Int. J. Mol. Sci. 2024, 25(4), 2196; https://doi.org/10.3390/ijms25042196 - 12 Feb 2024

Cited by 2 | Viewed by 1817

Abstract

Carbon–semiconductor hybrid quantum dots are classical carbon dots with core carbon nanoparticles doped with a selected nanoscale semiconductor. Specifically, on those with the nanoscale TiO₂ doping, denoted as C_TiO2-Dots, their synthesis and thorough characterization were reported previously. In this work, the C_TiO2-Dots were evaluated for their visible light-activated antibacterial function, with the results showing the effective killing of not only Gram-positive but also the generally more resistant Gram-negative bacteria. The hybrid dots are clearly more potent antibacterial agents than their neat carbon dot counterparts. Mechanistically, the higher antibacterial performance of the C_TiO2-Dots is attributed to their superior photoexcited state properties, which are reflected by the observed much brighter fluorescence emissions. Also considered and discussed is the possibility of additional contributions to the antibacterial activities due to the photosensitization of the nanoscale TiO₂ by its doped core carbon nanoparticles. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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Review

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20 pages, 976 KiB

Open AccessReview

Hypocrellin-Mediated PDT: A Systematic Review of Its Efficacy, Applications, and Outcomes

by Jakub Fiegler-Rudol, Katarzyna Kapłon, Kornela Kotucha, Magdalena Moś, Dariusz Skaba, Aleksandra Kawczyk-Krupka and Rafał Wiench

Int. J. Mol. Sci. 2025, 26(9), 4038; https://doi.org/10.3390/ijms26094038 - 24 Apr 2025

Abstract

Photodynamic therapy (PDT) is a light-activated treatment that generates reactive oxygen species (ROS) to induce microbial cell death. As resistance to traditional antibiotics intensifies globally, PDT has emerged as a promising alternative or adjunctive antimicrobial strategy. Among various photosensitizers, Hypocrellin, a perylenequinone compound, has shown high ROS yield and broad-spectrum activity against bacteria and fungi. This systematic review evaluated the efficacy, safety, and therapeutic potential of Hypocrellin-mediated antimicrobial photodynamic therapy. Following PRISMA 2020 guidelines, a comprehensive literature search was conducted in PubMed, Embase, Scopus, and the Cochrane Library for studies published between 2015 and 2025. Eligible studies included in vitro and preclinical in vivo research using Hypocrellin as a photosensitizer. Quality and risk of bias were assessed using a structured nine-item checklist. Ten eligible studies, all conducted in China, were included. Hypocrellin-mediated aPDT significantly reduced microbial loads in both planktonic and biofilm states of resistant pathogens such as Candida albicans, Candida auris, Cutibacterium acnes, and Staphylococcus aureus. The treatment acted via ROS-mediated apoptosis, membrane disruption, and mitochondrial dysfunction, with minimal cytotoxicity to mammalian cells. Studies also reported enhanced efficacy when Hypocrellin was incorporated into nanocarriers, polymeric scaffolds, or combined with chemodynamic or photothermal therapies. However, substantial heterogeneity was observed in Hypocrellin concentrations, irradiation parameters, and outcome measures. Hypocrellin-based PDT exhibits potent antimicrobial activity and favorable safety in preclinical settings, supporting its potential as an alternative to conventional antibiotics. However, standardized treatment protocols and robust clinical trials are urgently needed to validate long-term safety and translational feasibility. These findings underscore the broader promise of PDT in addressing drug-resistant infections through a mechanism unlikely to induce resistance. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

19 pages, 711 KiB

Open AccessReview

Toluidine Blue and Chlorin-e6 Mediated Photodynamic Therapy in the Treatment of Oral Potentially Malignant Disorders: A Systematic Review

by Anna Kruczek-Kazibudzka, Barbara Lipka, Jakub Fiegler-Rudol, Marcin Tkaczyk, Dariusz Skaba and Rafał Wiench

Int. J. Mol. Sci. 2025, 26(6), 2528; https://doi.org/10.3390/ijms26062528 - 12 Mar 2025

Cited by 2 | Viewed by 429

Abstract

Oral potentially malignant disorders (OPMDs) are conditions that carry an increased risk of malignant transformation, including oral leukoplakia and oral lichen planus. Current management approaches differ based on each condition’s unique etiology and pathophysiology, but all available treatment methods have notable limitations. This has prompted continued efforts to identify more effective therapeutic options. Photodynamic therapy (PDT) has emerged as a minimally invasive yet potent alternative for treating OPMDs. This systematic review examines the efficacy of PDT mediated by toluidine blue and chlorin-e6 (Photolon) in managing OPMDs. Following the PRISMA guidelines, eight relevant studies published between 2010 and 2024 were included. Data on the study design, protocols, light parameters, and photosensitizer characteristics were collected to evaluate treatment outcomes. The reviewed evidence suggests that toluidine-blue- and chlorin-e6-mediated PDT holds promise as a minimally invasive treatment modality for OPMDs, especially for oral lichen planus and oral leukoplakia. Studies indicate its potential as an alternative or adjunct therapy, particularly for symptomatic or refractory oral lichen planus. However, discrepancies in study designs and treatment protocols, coupled with the limited number of trials, impeded direct comparisons. Toluidine-blue- and chlorin-e6-mediated PDT shows significant potential as a therapeutic option for OPMDs. Nonetheless, further investigations—including large-scale randomized controlled trials, standardized treatment guidelines, and the exploration of additional OPMDs beyond oral lichen planus and oral leukoplakia—are necessary in order to fully establish its clinical utility and facilitate widespread adoption. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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9 pages, 507 KiB

Open AccessReview

Highways and Detours in the Realm of Photodynamic Therapy

by David Kessel and Qian Peng

Int. J. Mol. Sci. 2024, 25(6), 3119; https://doi.org/10.3390/ijms25063119 - 8 Mar 2024

Viewed by 1379

Abstract

Photodynamic therapy (PDT) has been a topic of interest since the first report in 1900 but has yet to become a ‘mainstream’ treatment protocol in the medical field. There are clear indications for which PDT might be the ‘method of choice’, but it is unlikely that there will be protocols for the treatment of systemic disease. This report discusses recent developments for promoting PDT efficacy, in the context of what is already known. Factors that can limit the scope of these applications are also indicated. Among the more interesting of these developments is the use of formulation techniques to target specific organelles for photodamage. This can enhance responses to PDT and circumvent situations where an impaired death pathway interferes with PDT efficacy. Full article

(This article belongs to the Special Issue Photodynamic Therapy and Photodetection, 2nd Edition)

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