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Photodynamic therapy – mechanisms, photosensitizers and combinations
Abstract
Photodynamic therapy (PDT) is a modern and non-invasive form of therapy, used in the treatment of non-oncological diseases as well as cancers of various types and locations. It is based on the local or systemic application of a photosensitive compound - the photosensitizer, which is accumulated in pathological tissues. The photosensitizer molecules absorb the light of the appropriate wavelength, initiating the activation processes leading to the selective destruction of the inappropriate cells. The photocytotoxic reactions occur only within the pathological tissues, in the area of photosensitizer distribution, enabling selective destruction. Over the last decade, a significant acceleration in the development of nanotechnology has been observed. The combination of photosensitizers with nanomaterials can improve the photodynamic therapy efficiency and eliminate its side effects as well. The use of nanoparticles enables achievement a targeted method which is focused on specific receptors, and, as a result, increases the selectivity of the photodynamic therapy. The object of this review is the anticancer application of PDT, its advantages and possible modifications to potentiate its effects.
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“PDT can produce ROS that induce tumor cell death by stimulating photosensitizers with specific wavelengths of therapeutic light [101–103].”
From Nanosensitizer-assisted sonodynamic therapy for breast cancer (2025) · cites this paper as [101]
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Photodynamic therapy-a promising treatment of oral mucosal infections
Chen, T., Yang, D., Lei, S., Liu, J., Song, Y., Zhao, H., Zeng, X. Y., Dan, H., & Chen, Q. (2022) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2022.103010 · Cited by 15
George, R. C., Torimiro, N., Daramola, O. B., & Olajide, A. A. (2022) · Ethiopian Journal of Science and Technology · doi:10.4314/ejst.v15i2.6 · Cited by 9
“Other radicals produced during the propagation stage are hydroxyl radicals (HO•) and hydroperoxyl radicals and all these species could kill an organism (Benov, 2015; Kwiatkowski et al., 2018; Niculescu and Grumezescu, 2021).”
BackgroundSinglet Oxygen In Vivo: It Is All about Intensity
Hackbarth, S., Islam, R., Šubr, V., Etrych, T., & Fang, J. (2022) · Journal of Personalized Medicine · doi:10.3390/jpm12060891 · Cited by 9
AlFawaz, Y. (2022) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2022.102912 · Cited by 9
Zuhayri, H., Nikolaev, V., Knyazkova, A., Lepekhina, T. B., Krivova, N., Tuchin, V., & Kistenev, Y. V. (2022) · Pharmaceutics · doi:10.3390/pharmaceutics14020287 · Cited by 9
“The latter causes the generation of reactive oxygen species (ROS) [14,20].”
BackgroundInfluentialSynthesis, Characterization and Biodistribution of GdF3:Tb3+@RB Nanocomposites
Polozhentsev, O., Pankin, I., Khodakova, D., Medvedev, P., Goncharova, A., Maksimov, A., Kit, O., & Soldatov, A. (2022) · Materials · doi:10.3390/ma15020569 · Cited by 9
He, Y.-Y., Duan, L., Wu, H., Chen, S., Lu, T., Li, T., & He, Y.-K. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.731414 · Cited by 9
“The intrinsicmechanism of PDT is the interaction between cellular components and reactive oxygen species (ROS), causing damage of cellular components and leading to cell apoptosis (14).”
BackgroundInfluentialCurrent Status of Photodynamic Diagnosis for Gastric Tumors
Kurumi, H., Kanda, T., Ikebuchi, Y., Yoshida, A., Kawaguchi, K., Yashima, K., & Isomoto, H. (2021) · Diagnostics · doi:10.3390/diagnostics11111967 · Cited by 9
“In addition, 5-ALA is more tumor-selective than Photofrin, Visudyne, and Laserphyrin, and is expected to reduce tissue damage (or side effect) to surrounding normal tissues [25].”
BackgroundTan, Y.-Z., Sun, S.-K., Chen, D., Qiu, H., Zeng, J., Wang, Y., Zhao, H.-Y., & Gu, Y. (2021) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2021.102320 · Cited by 9
Antimicrobial photodynamic therapy with hypocrellin B against SARS-CoV-2 infection?
Law, S. K., Lo, C., Han, J., Leung, A. W., & Xu, C. (2021) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2021.102297 · Cited by 9
Fuentes-Lemus, E., Mariotti, M., Hägglund, P., Leinisch, F., Fierro, A., Silva, E., Davies, M., & López-Alarcón, C. (2021) · Free Radical Biology & Medicine · doi:10.1016/j.freeradbiomed.2021.03.009 · Cited by 9
Zduniak, K., Gdesz-Birula, K., Woźniak, M., Duś-Szachniewicz, K., & Ziólkowski, P. (2020) · Molecules · doi:10.3390/molecules25215184 · Cited by 9
“The effects of combined therapy also enhanced 5-ALA-PDT therapy [17].”
BackgroundAndraos, C., & Gulumian, M. (2020) · Wiley Interdisciplinary Reviews: Nanomedicine and Nanobiotechnology · doi:10.1002/wnan.1680 · Cited by 9
“This interaction results in the production of free radicals and ROS or singlet oxygen (1O2) (Calixto, Bernegossi, de Freitas, Fontana, & Chorilli, 2016; Casais-Molina, Cab, Canto, Medina, & Tapia, 2018; Kwiatkowski et al., 2018; Yoo & Ha, 2012).”
BackgroundAnalysis of the short-term effect of photodynamic therapy on primary bronchial lung cancer
Lin, C.-Z., Zhang, Y., Zhao, Q., Sun, P., Gao, Z., & Cui, S.-C. (2020) · Lasers in Medical Science · doi:10.1007/s10103-020-03080-5 · Cited by 9
Photo Bio Stimulatory Effect of Low Dose Photodynamic Therapy on Human Mesenchymal Stem Cells.
Fekrazad, R., Asefi, S., Khorsandi, K., & Nejatifard, M. (2020) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2020.101886 · Cited by 9
Wu, R.-W.-K., Chu, E., & Yow, C. (2020) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2020.101801 · Cited by 9
Nag, S., Bagchi, D., Chattopadhyay, D., Bhattacharyya, M., & Pal, S. K. (2020) · International Journal of Pharmaceutics · doi:10.1016/j.ijpharm.2020.119192 · Cited by 9
Isaac-Lam, M. F., & Hammonds, D. M. (2019) · ACS Omega · doi:10.1021/acsomega.9b02394 · Cited by 15
Hu, L., Han, H., Xu, Z., Song, K., & Wang, F. (2023) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2023.136007 · Cited by 10
Development of fullerene nanospherical miRNA and application in overcoming resistant breast cancer
Xu, J.-R., Xie, Y., Li, J.-W., Liu, R., Chen, M., Ren, Y.-X., Luo, Q., Duan, J., Bao, C., Liu, Y.-X., et al. (2022) · Materials Today Chemistry · doi:10.1016/j.mtchem.2022.101019 · Cited by 9
Shi, B., Hua, J., Huang, C., Xiong, R., & Miao, D. (2026) · Journal of Photochemistry and Photobiology C Photochemistry Reviews · doi:10.1016/j.jphotochemrev.2026.100736 · Cited by 10
Recent advances in ROS-modulating materials for sepsis treatment
Mo, X. W., Min, D. K., & Kim, J. (2026) · Journal of Controlled Release · doi:10.1016/j.jconrel.2026.114779 · Cited by 9
A third-generation rhodium-based nanophotosensitizer for precision photodynamic cancer therapy.
Machuca, A., García, R. Á.-F., Garcia-Garcia, A., Aragoneses-Cazorla, G., Castillo-Lluva, S., Vallet-Regí, M., González, B., García-Calvo, E., & Luque-Garcia, J. (2026) · Journal of Colloid and Interface Science · doi:10.1016/j.jcis.2026.140143 · Cited by 8
Kim, M., & Hong, J. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010066 · Cited by 8
Pashootan, P., González‐Valdivieso, J., Moosavi, M. A., Fernández‐Lucas, J., Cordani, M., Zarepour, A., Khosravi, A., Fangano, G., Petralia, S., Iravani, S., et al. (2025) · Inorganic Chemistry Communications · doi:10.1016/j.inoche.2025.115637 · Cited by 8
Zheng, W.-T., Chen, H.-L., Hou, X.-T., Abakirova, A., Han, M.-Y., Feng, Y.-Q., Huang, W.-T., Mo, X.-C., Zhu, H.-C., Huang, S.-K., et al. (2025) · Discover Nano · doi:10.1186/s11671-025-04402-8 · Cited by 8
Pourhajibagher, M., Bahrami, R., & Bahador, A. (2025) · Journal of lasers in medical sciences · doi:10.34172/jlms.2025.33 · Cited by 8
Ortiz-Islas, E., Manríquez-Ramírez, M. E., Montes, P., Rodríguez-Pérez, C. E., Ruiz-Sánchez, E., Carvajal, K., & Campos‐Peña, V. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17091132 · Cited by 9
Gas Plasma Combination Therapies—Promises from Preclinical Oncology Research
Yu, L., Berner, J., Martinet, A., Freund, E., Singer, D., von Woedtke, T., Weltmann, K., Emmert, S., Clemen, R., & Bekeschus, S. (2025) · Antioxidants · doi:10.3390/antiox14091055 · Cited by 7
“Photodynamic reactions involve type 1-generating O 2 •− and type 2-producing 1 O 2, essential in anticancer effects [185].”
ROS-mediated cell death and phase separation in gynecological malignancies
Wei, H., Xiong, M., & Min, L. (2025) · European journal of medical research · doi:10.1186/s40001-025-02846-3 · Cited by 10
Liang, J., Wu, Y. B., Zhang, C., Yi, R., Zheng, J., Zhao, R., Shan, D., & Wang, B. (2025) · International Journal of Nanomedicine · doi:10.2147/ijn.s516606 · Cited by 12
Nkune, N. W., & Abrahamse, H. (2025) · Journal of Biophotonics · doi:10.1002/jbio.70005 · Cited by 9
Ferreira, A. S., de Almeida, A. M., Kobal, M. B., Moreira, L. G., Camacho, S. A., de Toledo, K. A., Oliveira, O. N., DeWolf, C. E., & Aoki, P. H. B. (2025) · Langmuir · doi:10.1021/acs.langmuir.4c05013 · Cited by 8
Liao, Y., Lin, X., He, Z., Chen, J., Tang, S., Wang, W., & Chen, W. (2024) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2024.108022 · Cited by 11
Molecular Biomarkers in Cutaneous Photodynamic Therapy: A Comprehensive Review
Naharro‐Rodríguez, J., Bacci, S., & Fernández-Guarino, M. (2024) · Diagnostics · doi:10.3390/diagnostics14232724 · Cited by 8
“This approach is indicated for non-high-risk tumoral lesions with an excellent cosmetic result [1,2].”
Application of Peptide-Conjugated Photosensitizers for Photodynamic Cancer Therapy: A Review
Vale, N., Ramos, R., Cruz, I., & Pereira, M. (2024) · Organics · doi:10.3390/org5040022 · Cited by 7
“These were achieved by conjugating them with targeting entities or moieties, such as carbohydrates, antibodies, peptides, and amino acids, or by encapsulation into carriers [1,6,15,24,26].”
A Review of Non-Linear Optical Imaging Techniques for Cancer Detection
Ávila, F. J. (2024) · Optics · doi:10.3390/opt5040031 · Cited by 9
Yeo, S., Wu, H., Yoon, I., Kim, H.-S., Song, Y. K., & Lee, W. K. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910382 · Cited by 7
“The lipoproteins acting as transporters could combine with PSs and facilitate the delivery of PSs to the area of the tumor rather than normal cells [7–9].”
BackgroundTumor oxygenation nanoliposomes promote deep photodynamic therapy for triple-negative breast cancer
Han, J., Xu, X., Jin, F., Xu, X., Fang, T., & Du, Y. (2024) · Biomaterials Science · doi:10.1039/d4bm00847b · Cited by 12
“51 To address the challenges of limited tissue penetration and potential toxic e ff ects, there has been growing interest in near-infrared light-sensitive photosensitizers.”
BackgroundLiu, R., & Qian, Y. (2024) · Organic & Biomolecular Chemistry · doi:10.1039/d4ob00706a · Cited by 13
Wang, Y., Chen, J., Zhang, Z., Ding, X., Gan, J., Guo, Y., Liang, W., Wang, Y., Deng, Y., & Sun, A. (2024) · Frontiers in Medicine · doi:10.3389/fmed.2024.1388045 · Cited by 8
“Photodynamic therapy is based on the possibility of selectively destroying pathological tissue by using accumulated photosensitizers (30), namely stimulating uterine tissue cells, soothing uterine smooth muscle, restoring blood circulation of uterine tissue and enhancing the metabolism of damaged…”
BackgroundBibliometric analysis of photodynamic therapy and immune response from 1989–2023
Fan, W., Tang, J., Tang, S., Lin, Z., Li, M., Zhang, Z., & Wu, D. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1299253 · Cited by 6
“All of these vary according to the lesion site and condition of the speci fi c treatment, but they are generally not serious, their duration is short, and most can be alleviated by conventional management (Kwiatkowski et al., 2018).”
BackgroundAn AIE Metal Iridium Complex: Photophysical Properties and Singlet Oxygen Generation Capacity
Zhu, W., Liu, S., Wang, Z., Shi, C., Zhang, Q., Wu, Z., Li, G., & Zhu, D. (2023) · Molecules · doi:10.3390/molecules28237914 · Cited by 10
“Photodynamic therapy is a selective process in which photosensitizer molecules absorb the appropriate wavelength of light and initiate the photoactivation process to produce toxic substances, thus leading to apoptosis or necrosis of pathological tissue cells [1,2].”
BackgroundChakraborty, N., Jha, D., Singh, V. P., Kumar, P., Verma, N., Gautam, H., & Roy, I. (2023) · ACS Applied Materials and Interfaces · doi:10.1021/acsami.3c09516 · Cited by 8
Xia, Q., Shen, J., Ding, H., Liu, S., Li, F., Li, F., & Feng, N. (2023) · Expert Opinion on Drug Delivery · doi:10.1080/17425247.2023.2268512 · Cited by 8
“Photodynamic therapy was found to be selective to tumor cells, possibly due to the higher metabolic rates [160].”
BackgroundTavares, M. R., Islam, R., Šubr, V., Hackbarth, S., Gao, S., Yang, K., Lobaz, V., Fang, J. Q., & Etrych, T. (2023) · Theranostics · doi:10.7150/thno.86211 · Cited by 12
“PDT uses light as external stimuli to activate photosensitizer molecules (PSs) and oxygen to generate cytotoxic reactive oxygen species (ROS) such as peroxide, singlet oxygen ( 1 O 2 ), and hydroxyl species [3, 4].”
Lee, S., Chung, M. J., Ahn, M., Park, H. J., Wang, E. K., Guon, T., Kee, H. J., Ku, C. R., & Na, K. (2023) · Biomaterials · doi:10.1016/j.biomaterials.2023.122336 · Cited by 9
Yan, S., Dong, L., Hu, Z., Zhang, Y., Xu, W. J., Xing, J., & Zhang, J. (2023) · Molecules · doi:10.3390/molecules28155874 · Cited by 8
Nanocarriers for photodynamic-gene therapy
de Santana, W. M. O. S., Surur, A. K., Momesso, V. M., Lopes, P. M., Santilli, C. V., & Fontana, C. R. (2023) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2023.103644 · Cited by 10
Borissevitch, I. E., Silveira-Alves, E., de Almeida, C. G. L., de Souza, G. R. L., Sokolov, S. S., & Gonçalves, P. J. (2023) · Photonics · doi:10.3390/photonics10040409 · Cited by 11
Henriques, J., Pina, J., Braga, M. E., Dias, A. M. A., Coimbra, P., & de Sousa, H. D. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15041080 · Cited by 8
“Photodynamic therapy (PDT) is a biomedical therapeutic approach that combines three components that alone usually do not elicit a toxic response in biological systems: a photosensitive compound, a light source with a well-defined wavelength, and molecular oxygen (O2) [1,2].”
BackgroundZuhayri, H., Samarinova, A. A., Borisov, A., Guardado, D. A. L., Baalbaki, H., Krivova, N., & Kistenev, Y. V. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15020595 · Cited by 8
“Phospholipids are the major targets sensitive to radicals and ROSs [62], which can be generated by LDPDT [23,63].”
BackgroundShi, X., Yin, H., Dong, X., Li, H., & Li, Y. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1062666 · Cited by 10
“In PDT, photosensitizers are first injected into patients or used to cover the surface of the skin for a certain time to selectively combine with tumor tissues, and then light of a specific wavelength is used to initiate a photochemical reaction with tissue oxygen to generate reactive oxygen species (ROS), which acts…”
BackgroundDias, L. D., Duarte, L. S., Naves, P. L. F., Napolitano, H. B., & Bagnato, V. S. (2022) · Microorganisms · doi:10.3390/microorganisms10122484 · Cited by 10
“This mechanism of action can undergo two pathways and generate two groups of ROS: (i) H2O2 (hydrogen peroxide); O2 (superperoxide anion); OH (hydroxyl radical) (Type I mechanism); (ii) (1)O2 (singlet oxygen) (type II mechanism), as described in Figure 2 [28].”
BackgroundMethodKarayianni, M., Koufi, D., & Pispas, S. (2022) · Polymers · doi:10.3390/polym14235186 · Cited by 8
“These include high chemical purity, stability at room temperature, high photochemical reactivity, minimum dark cytotoxicity, preferential retention at the targeted tissue, facile solubility in bodily fluids, low cost, and wide availability, among others [2,3].”
BackgroundLight-Activated Phytochemicals in Photodynamic Therapy for Cancer: A Mini Review
George, B., & Abrahamse, H. (2022) · Photobiomodulation, photomedicine, and laser surgery · doi:10.1089/photob.2022.0094 · Cited by 8
“The ratio of the input of type I and type II reactions largely rely on several factors such as concentration of oxygen, dielectric constant, pH of the tissue, and structure of PSs. 30,34 The subcellular localization of PS is an important factor in enhancing PDT efficiency.”
5-Aminolevulinic Acid and Red Led in Endodontics: A Narrative Review and Case Report
D'Ercole, S., Carlesi, T., Dotta, T. C., Pierfelice, T., D'Amico, E., Tripodi, D., Iezzi, G., Piattelli, A., & Petrini, M. (2022) · Gels · doi:10.3390/gels8110697 · Cited by 8
Reactive oxygen specie-induced photodynamic therapy activation by supramolecular strategy
Wang, S., Zhao, Z.-Z., Yao, J., Jiang, S., Li, Z.-T., & Ma, D. (2022) · Chinese Chemical Letters · doi:10.1016/j.cclet.2022.107805 · Cited by 8
Smart intraoral systems for advanced drug delivery
Liu, Y., Guo, H., Xu, R., & Chen, W. (2022) · MedComm – Biomaterials and Applications · doi:10.1002/mba2.19 · Cited by 10
Özçelik, Ş., Yurttaş, A., Kahveci, M. U., Sevim, A., & Gül, A. (2022) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2022.134019 · Cited by 8
Treatment of Actinic Keratosis: The Best Choice through an Observational Study
Yoo, S. A., Kim, Y. H., Han, J. H., Bang, C. H., Park, Y. M., & Lee, J.-H. (2022) · Journal of Clinical Medicine · doi:10.3390/jcm11143953 · Cited by 8
“PDT is one of the approved procedural field therapies [5,6,10].”
BackgroundLin, H.-H., Yang, X.-Z., Yu, M.-Y., & Liu, J. (2022) · Dyes and Pigments · doi:10.1016/j.dyepig.2022.110217 · Cited by 9
Metadata
- Authors
- Kwiatkowski, S., Knap, B., Przystupski, D., Saczko, J., Kędzierska, E., Knap-Czop, K., Kotlińska, J., Michel, O., Kotowski, K., & Kulbacka, J.
- Affiliations
- Wroclaw Medical University (PL)
- Medical University of Lublin (PL)
- Corresponding author
- Kulbacka, Julita
- ORCID
- Venue
- Biomedicine & Pharmacotherapy
- Publisher
- Elsevier BV
- Published
- 2018-10
- Volume
- 106
- Pages
- 1098-1107
- ISSN
- 0753-3322 (ISSN-L)
- OpenAlex
- W2884145325
- Cited by
- 2,173
- References
- 0
- Citations by year
- 2026: 192 · 2025: 360 · 2024: 404 · 2023: 362 · 2022: 340 · 2021: 272 · 2020: 174 · 2019: 61 · 2018: 7
- FWCI
- 22.96
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- Biomedicine & Pharmacotherapy (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uniwersytet Medyczny im. Piastów Slaskich we Wroclawiu
- Uniwersytet Medyczny w Lublinie
- Servier
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Photodynamic Therapy Research Studies
- Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- photodynamic therapy, photosensitizers, photocytotoxicity, targeted drug delivery, nanoparticles, nanomaterials, combination therapy
- MeSH terms
- Animals, Drug Carriers, Humans, Neoplasms, Photochemotherapy, Drug Delivery Systems, Photosensitizing Agents, Nanomedicine, Electrochemotherapy, Nanoparticles
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