Photodynamic Therapy in Cancer: Principles, State of the Art, and Future Directions

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Targeting and Design".

Deadline for manuscript submissions: 20 August 2024 | Viewed by 4870

Special Issue Editors


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Guest Editor
1. Cell Death Investigation and Therapy Laboratory, Department of Human Structure and Repair, Ghent University, 9000 Ghent, Belgium
2. Cancer Research Institute Ghent, 9000 Ghent, Belgium
Interests: immunogenic cell death; photodynamic therapy; cancer immunotherapy

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Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., Nizhny Novgorod 603022, Russia
Interests: cancer cell biology; photodynamic therapy; targeted therapy; nanomedicine
Special Issues, Collections and Topics in MDPI journals

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Institute of Biology and Biomedicine, Lobachevsky State University of Nizhny Novgorod, 23 Gagarin Ave., 603022 Nizhny Novgorod, Russia
Interests: brain cancer; photodynamic-driven cancer immunotherapy; immunogenic cell death

Special Issue Information

Dear Colleagues,

Since its discovery more than 100 years ago, photodynamic therapy (PDT) has become a potent strategy for the treatment of many types of cancer. Studies in recent years have allowed the deciphering of many aspects of cell response to PDT and a shift from the view of PDT as the oxidative stress inducer to understanding the complexity of molecular mechanisms controlling cell death and survival under PDT treatment. Moreover, in the past decade, it has become clear that the efficacy of PDT depends largely on the ability to induce immunogenic cell death that enables the activation of the immune system to induce efficient anticancer immunity with long-lasting immunological memory. This Special Issue aims to gather state-of-the-art research articles and comprehensive reviews focusing on the recent progress in discovering the PDT mechanisms and, based on this knowledge, the development of novel PDT agents, protocols, and strategies. Research areas may include, but are not limited to, the following:

  • New PDT agents: on the way to the “ideal” photosensitizer
  • Personalized photodynamic therapy
  • Targeted systems for photodynamic therapy of cancer
  • Nano-based agents and materials for photodynamic therapy of cancer
  • Novel approaches in oxygen-boosted photodynamic therapy of cancer
  • Combination of PDT with other anticancer treatment strategies
  • Photochemistry of PDT-induced damages
  • Molecular mechanisms of cell response to the photodynamic therapy of cancer
  • Cancer cell death modalities induced by photodynamic therapy
  • Immunogenic cell death and photodynamic therapy of cancer
  • PDT-driven cancer immunotherapy
  • Bystander effects in photodynamic therapy of cancer
  • Cancer cells trick to overcome PDT efficiency and how to fight cancer resistance
  • Current clinical trials in PDT of cancer

Dr. Dmitri V. Krysko
Dr. Irina V. Balalaeva
Dr. Tatiana A. Mishchenko
Guest Editors

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Keywords

  • anticancer photodynamic therapy
  • photosensitizers
  • photochemical damage
  • nano-drugs
  • drug delivery
  • PDT-induced cell death modalities
  • immunogenic cell death
  • tumor hypoxia
  • bystander effect
  • tumor resistance
  • clinical trials in PDT

Published Papers (5 papers)

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Research

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19 pages, 4137 KiB  
Article
Investigation of Photodynamic Therapy Promoted by Cherenkov Light Activated Photosensitizers—New Aspects and Revelations
by Lisa Hübinger, Kerstin Wetzig, Roswitha Runge, Holger Hartmann, Falk Tillner, Katja Tietze, Marc Pretze, David Kästner, Robert Freudenberg, Claudia Brogsitter and Jörg Kotzerke
Pharmaceutics 2024, 16(4), 534; https://doi.org/10.3390/pharmaceutics16040534 - 13 Apr 2024
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Abstract
This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used [...] Read more.
This work investigates the proposed enhanced efficacy of photodynamic therapy (PDT) by activating photosensitizers (PSs) with Cherenkov light (CL). The approaches of Yoon et al. to test the effect of CL with external radiation were taken up and refined. The results were used to transfer the applied scheme from external radiation therapy to radionuclide therapy in nuclear medicine. Here, the CL for the activation of the PSs (psoralen and trioxsalen) is generated by the ionizing radiation from rhenium-188 (a high-energy beta-emitter, Re-188). In vitro cell survival studies were performed on FaDu, B16 and 4T1 cells. A characterization of the PSs (absorbance measurement and gel electrophoresis) and the CL produced by Re-188 (luminescence measurement) was performed as well as a comparison of clonogenic assays with and without PSs. The methods of Yoon et al. were reproduced with a beam line at our facility to validate their results. In our studies with different concentrations of PS and considering the negative controls without PS, the statements of Yoon et al. regarding the positive effect of CL could not be confirmed. There are slight differences in survival fractions, but they are not significant when considering the differences in the controls. Gel electrophoresis showed a dominance of trioxsalen over psoralen in conclusion of single and double strand breaks in plasmid DNA, suggesting a superiority of trioxsalen as a PS (when irradiated with UVA). In addition, absorption measurements showed that these PSs do not need to be shielded from ambient light during the experiment. An observational test setup for a PDT nuclear medicine approach was found. The CL spectrum of Re-188 was measured. Fluctuating inconclusive results from clonogenic assays were found. Full article
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10 pages, 746 KiB  
Article
Photodynamic Therapy Supported by Antitumor Lipids
by Mladen Korbelik
Pharmaceutics 2023, 15(12), 2723; https://doi.org/10.3390/pharmaceutics15122723 - 03 Dec 2023
Viewed by 843
Abstract
Photodynamic therapy (PDT) destroys tumors by generating cytotoxic oxidants that induce oxidative stress in targeted cancer cells. Antitumor lipids developed for cancer therapy act also by inflicting similar stress. The present study investigated whether tumor response to PDT can be improved by adjuvant [...] Read more.
Photodynamic therapy (PDT) destroys tumors by generating cytotoxic oxidants that induce oxidative stress in targeted cancer cells. Antitumor lipids developed for cancer therapy act also by inflicting similar stress. The present study investigated whether tumor response to PDT can be improved by adjuvant treatment with such lipids using the prototype molecule edelfosine. Cellular stress intensity following Photofrin-based PDT, edelfosine treatment, or their combination was assessed by the expression of heat shock protein 70 (HSP70) on the surface of treated SCCVII tumor cells by FITC-conjugated anti-HSP70 antibody staining and flow cytometry. Surface HSP70 levels that became elevated after either PDT or edelfosine rose much higher after their combined treatment. The impact of Photofrin-PDT-plus-edelfosine treatment was studied with three types of tumor models grown in syngeneic mice. With both SCCVII squamous cell carcinomas and MCA205 fibrosarcoma, the greatest impact was with edelfosine peritumoral injection at 24 h after PDT, which substantially improved tumor cure rates. With Lewis lung carcinomas, edelfosine was highly effective in elevating PDT-mediated tumor cure rates even when injected peritumorally immediately after PDT. Edelfosine used before PDT was ineffective as adjuvant with all tumor models. The study findings provide proof-in-principle for use of cancer lipids with tumor PDT. Full article
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17 pages, 2126 KiB  
Article
Dendritic Cells Pulsed with Tumor Lysates Induced by Tetracyanotetra(aryl)porphyrazines-Based Photodynamic Therapy Effectively Trigger Anti-Tumor Immunity in an Orthotopic Mouse Glioma Model
by Tikhon S. Redkin, Ekaterina E. Sleptsova, Victoria D. Turubanova, Mariia O. Saviuk, Svetlana A. Lermontova, Larisa G. Klapshina, Nina N. Peskova, Irina V. Balalaeva, Olga Krysko, Tatiana A. Mishchenko, Maria V. Vedunova and Dmitri V. Krysko
Pharmaceutics 2023, 15(10), 2430; https://doi.org/10.3390/pharmaceutics15102430 - 06 Oct 2023
Cited by 3 | Viewed by 1419
Abstract
Research in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and [...] Read more.
Research in the past decade on immunogenic cell death (ICD) has shown that the immunogenicity of dying tumor cells is crucial for effective anticancer therapy. ICD induction leads to the emission of specific damage-associated molecular patterns (DAMPs), which act as danger signals and as adjuvants to activate specific anti-tumor immune responses, leading to the elimination of tumor cells and the formation of long-term immunological memory. ICD can be triggered by many anticancer treatment modalities, including photodynamic therapy (PDT). However, due to the variety of photosensitizers used and the lack of a universally adopted PDT protocol, there is a need to develop novel PDT with a proven ICD capability. In the present study, we characterized the abilities of two photoactive dyes to induce ICD in experimental glioma in vitro and in vivo. One dye was from the tetracyanotetra(aryl)porphyrazine group with 9-phenanthrenyl (pz I), and the other was from the 4-(4-fluorobenzyoxy)phenyl (pz III) group in the aryl frame of the macrocycle. We showed that after the photosensitizers penetrated into murine glioma GL261 cells, they localized predominantly in the Golgi apparatus and partially in the endoplasmic reticulum, providing efficient phototoxic activity against glioma GL261 cells upon light irradiation at a dose of 20 J/cm2 (λex 630 nm; 20 mW/cm2). We demonstrated that pz I-PDT and pz III-PDT can act as efficient ICD inducers when applied to glioma GL261 cells, facilitating the release of two crucial DAMPs (ATP and HMGB1). Moreover, glioma GL261 cells stimulated with pz I-PDT or pz III-PDT provided strong protection against tumor growth in a prophylactic subcutaneous glioma vaccination model. Finally, we showed that dendritic cell (DC) vaccines pulsed with the lysates of glioma GL261 cells pre-treated with pz-I-PDT or pz-III-PDT could act as effective inducers of adaptive anti-tumor immunity in an intracranial orthotopic glioma mouse model. Full article
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17 pages, 5489 KiB  
Article
Penetration of Nanobody-Dextran Polymer Conjugates through Tumor Spheroids
by Peter Bitsch, Eva S. Baum, Irati Beltrán Hernández, Sebastian Bitsch, Jakob Harwood, Sabrina Oliveira and Harald Kolmar
Pharmaceutics 2023, 15(10), 2374; https://doi.org/10.3390/pharmaceutics15102374 - 22 Sep 2023
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Abstract
Here we report the generation of nanobody dextran polymer conjugates (dextraknobs) that are loaded with small molecules, i.e., fluorophores or photosensitizers, for potential applications in cancer diagnostics and therapy. To this end, the molecules are conjugated to the dextran polymer which is coupled [...] Read more.
Here we report the generation of nanobody dextran polymer conjugates (dextraknobs) that are loaded with small molecules, i.e., fluorophores or photosensitizers, for potential applications in cancer diagnostics and therapy. To this end, the molecules are conjugated to the dextran polymer which is coupled to the C-terminus of an EGFR-specific nanobody using chemoenzymatic approaches. A monovalent EGFR-targeted nanobody and biparatopic version modified with different dextran average molecular weights (1000, 5000, and 10,000) were probed for their ability to penetrate tumor spheroids. For monovalent Cy5-labeled dextraknobs, the utilization of smaller sized dextran (MW 5000 vs. 10,000) was found to be beneficial for more homogeneous penetration into A431 tumor spheroids over time. For the biparatopic dual nanobody comprising MW 1000, 5000, and 10,000 dextran labeled with photosensitizer IRDye700DX, penetration behavior was comparable to that of a direct nanobody-photosensitizer conjugate lacking a dextran scaffold. Additionally, dextraknobs labeled with IRDye700DX incubated with cells in 2D and 3D showed potent cell killing upon illumination, thus inducing photodynamic therapy (PDT). In line with previous results, monovalent nanobody conjugates displayed deeper and more homogenous penetration through spheroids than the bivalent conjugates. Importantly, the smaller size dextrans did not affect the distribution of the conjugates, thus encouraging further development of dextraknobs. Full article
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Review

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50 pages, 28405 KiB  
Review
Enhancing Precision in Photodynamic Therapy: Innovations in Light-Driven and Bioorthogonal Activation
by Natalia S. Kuzmina, Ekaterina A. Fedotova, Petar Jankovic, Galina P. Gribova, Alexander V. Nyuchev, Alexey Yu. Fedorov and Vasilii F. Otvagin
Pharmaceutics 2024, 16(4), 479; https://doi.org/10.3390/pharmaceutics16040479 - 31 Mar 2024
Viewed by 552
Abstract
Over the past few decades, photodynamic therapy (PDT) has evolved as a minimally invasive treatment modality offering precise control over cancer and various other diseases. To address inherent challenges associated with PDT, researchers have been exploring two promising avenues: the development of intelligent [...] Read more.
Over the past few decades, photodynamic therapy (PDT) has evolved as a minimally invasive treatment modality offering precise control over cancer and various other diseases. To address inherent challenges associated with PDT, researchers have been exploring two promising avenues: the development of intelligent photosensitizers activated through light-induced energy transfers, charges, or electron transfers, and the disruption of photosensitive bonds. Moreover, there is a growing emphasis on the bioorthogonal delivery or activation of photosensitizers within tumors, enabling targeted deployment and activation of these intelligent photosensitive systems in specific tissues, thus achieving highly precise PDT. This concise review highlights advancements made over the last decade in the realm of light-activated or bioorthogonal photosensitizers, comparing their efficacy and shaping future directions in the advancement of photodynamic therapy. Full article
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