Current Challenges and Opportunities of Photodynamic Therapy against Cancer

Huis in ‘t Veld, Ruben V.; Heuts, Jeroen; Ma, Sen; Cruz, Luis J.; Ossendorp, Ferry A.; Jager, Martine J.

doi:10.3390/pharmaceutics15020330

Cited by 159Photodynamic Therapy Research StudiesNanoplatforms for cancer theranosticsNonmelanoma Skin Cancer Studies

Current Challenges and Opportunities of Photodynamic Therapy against Cancer

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Huis in ‘t Veld, Ruben V., Heuts, Jeroen, Ma, Sen, Cruz, Luis J., Ossendorp, Ferry A., Jager, Martine J.·2023·Pharmaceutics

DOI 10.3390/pharmaceutics15020330PMC PMC9965442

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Abstract

BACKGROUND: Photodynamic therapy (PDT) is an established, minimally invasive treatment for specific types of cancer. During PDT, reactive oxygen species (ROS) are generated that ultimately induce cell death and disruption of the tumor area. Moreover, PDT can result in damage to the tumor vasculature and induce the release and/or exposure of damage-associated molecular patterns (DAMPs) that may initiate an antitumor immune response. However, there are currently several challenges of PDT that limit its widespread application for certain indications in the clinic. METHODS: A literature study was conducted to comprehensively discuss these challenges and to identify opportunities for improvement. RESULTS: The most notable challenges of PDT and opportunities to improve them have been identified and discussed. CONCLUSIONS: The recent efforts to improve the current challenges of PDT are promising, most notably those that focus on enhancing immune responses initiated by the treatment. The application of these improvements has the potential to enhance the antitumor efficacy of PDT, thereby broadening its potential application in the clinic.

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PDT produces ROS that cause oxidative damage to targeted cells, including bacteria, fungi, parasites, viruses, and cancer cells, without significantly harming healthy tissues.
“This combination produces ROS, which can cause oxidative damage to targeted cells, including bacteria, fungi, parasites, viruses, and cancer cells, without significantly harming healthy tissues [134,135].”
From Emerging Applications of Chlorella sp. and Spirulina (Arthrospira) sp. (2023) · cites this paper as [134]
The Introduction says PDT generates ROS that can initiate cell death, and Section 4 describes damage to tumor cells. Section 4.2 reports that vessels surrounding a treated tumor area remained intact in one setting, but it does not establish that healthy tissues generally avoid significant harm. The cited passages do not support the added list of bacteria, fungi, parasites, and viruses as targeted cells. (LLM, conf=0.88)
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Cyclometalated Iridium(III)-Complex-Based Micelles for Glutathione-Responsive Targeted Chemotherapy and Photodynamic Therapy
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Combination of Photodynamic Therapy and Specific Immunotherapy Efficiently Eradicates Established Tumors
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Photodynamic Therapy Induced Enhancement of Tumor Vasculature Permeability Using an Upconversion Nanoconstruct for Improved Intratumoral Nanoparticle Delivery in Deep Tissues
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Release of Cytochrome c, Bax Migration, Bid Cleavage, and Activation of Caspases 2, 3, 6, 7, 8, and 9 during Endothelial Cell Apoptosis
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Systemic Antitumor Immunity by PD-1/PD-L1 Inhibition Is Potentiated by Vascular-Targeted Photodynamic Therapy of Primary Tumors
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Near-Infrared Light-Activated Photochemical Internalization of Reduction-Responsive Polyprodrug Vesicles for Synergistic Photodynamic Therapy and Chemotherapy
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Photodynamic-therapy Activates Immune Response by disrupting Immunity Homeostasis of Tumor Cells, which Generates Vaccine for Cancer Therapy
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Current Advances in Photodynamic Therapy (PDT) and the Future Potential of PDT-Combinatorial Cancer Therapies
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Photodynamic therapy for cancer: mechanisms, photosensitizers, nanocarriers, and clinical studies
Zhao, W., Wang, L., Zhang, M., Liu, Z., Wu, C., Pan, X., Huang, Z., Lu, C. T., & Quan, G. (2024) · MedComm · doi:10.1002/mco2.603 · Cited by 172 · see citing works
Emerging nitric oxide gas‐assisted cancer photothermal treatment
Liang, S., Liu, Y., Zhu, H., Liao, G., Zhu, W., & Zhang, L. (2024) · Exploration · doi:10.1002/exp.20230163 · Cited by 135 · see citing works
Emerging Applications of Chlorella sp. and Spirulina (Arthrospira) sp.
Abreu, A. P., Martins, R., & Nunes, J. (2023) · Bioengineering · doi:10.3390/bioengineering10080955 · Cited by 119 · see citing works
A Comprehensive Review of Inorganic Sonosensitizers for Sonodynamic Therapy
Chen, P., Zhang, P., Shah, N. H., Cui, Y., & Wang, Y. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512001 · Cited by 82 · see citing works
Enhancing cancer immunotherapy with photodynamic therapy and nanoparticle: making tumor microenvironment hotter to make immunotherapeutic work better
Thiruppathi, J., Vijayan, V., Park, I., Lee, S. E., & Rhee, J. H. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1375767 · Cited by 81 · see citing works
Recent Progress of Molecular Design in Organic Type I Photosensitizers
Xiong, T., Chen, Y., Li, M., Chen, X., & Peng, X. (2025) · Small · doi:10.1002/smll.202501911 · Cited by 77 · see citing works
Photodynamic Therapy in the Treatment of Cancer—The Selection of Synthetic Photosensitizers
Aebisher, D., Serafin, I., Batóg-Szczęch, K., Dynarowicz, K., Chodurek, E., Kawczyk‐Krupka, A., & Bartusik‐Aebisher, D. (2024) · Pharmaceuticals · doi:10.3390/ph17070932 · Cited by 72 · see citing works
Hypoxia: syndicating triple negative breast cancer against various therapeutic regimens
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Inducing Immunogenic Cancer Cell Death through Oxygen‐Economized Photodynamic Therapy with Nitric Oxide‐Releasing Photosensitizers
Xu, F., Wang, M., Dotse, E., Chow, K. T., & Lo, P. (2024) · Angewandte Chemie International Edition · doi:10.1002/anie.202404561 · Cited by 63 · see citing works
Gold nanoparticle-mediated photothermal therapy: Expanding the frontiers of cancer treatment and theragnostics
Amaral, M., Kumar, P., Faísca, P., Ferreira, H. A., Coelho, J. M. P., Gaspar, M. M., & Reis, C. P. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118399 · Cited by 62 · see citing works
Photodynamic Therapy for Colorectal Cancer: An Update and a Look to the Future
Rodrigues, J. A., & Correia, J. H. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241512204 · Cited by 59 · see citing works
Recent Advances in Reprogramming Strategy of Tumor Microenvironment for Rejuvenating Photosensitizers‐Mediated Photodynamic Therapy
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Nanoparticle-based drug delivery systems to enhance cancer immunotherapy in solid tumors
Zhang, J., Wang, S., Zhang, D. D., He, X., Wang, X. B., Han, H., & Qin, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1230893 · Cited by 56 · see citing works
Metal-based nanoparticles in cancer therapy: Exploring photodynamic therapy and its interplay with regulated cell death pathways
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Advances in the Design of Photoactivatable Metallodrugs: Excited State Metallomics
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Nanotechnology in leukemia therapy: revolutionizing targeted drug delivery and immune modulation
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Recent Advances in Photodynamic Therapy: Metal-Based Nanoparticles as Tools to Improve Cancer Therapy
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Recent Advances in Hydrogel-Based Phototherapy for Tumor Treatment
Gan, S., Wu, Y., Zhang, X., Zheng, Z., Zhang, M., Li, L., Liao, J., & Chen, W. (2023) · Gels · doi:10.3390/gels9040286 · Cited by 38 · see citing works
Metronomic Photodynamic Therapy with Conjugated Polymer Nanoparticles in Glioblastoma Tumor Microenvironment
Caverzán, M. D., Oliveda, P. M., Beaugé, L., Palacios, R. E., Chesta, C. A., & Ibarra, L. E. (2023) · Cells · doi:10.3390/cells12111541 · Cited by 37 · see citing works
Carbon-based nanomaterials in photodynamic therapy of cancer
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Photoacid Generators for Biomedical Applications
Sun, T., Kang, L., Zhao, H., Zhao, Y., & Gu, Y. (2023) · Advanced Science · doi:10.1002/advs.202302875 · Cited by 32 · see citing works
Overcoming challenges in cancer treatment: Nano‐enabled photodynamic therapy as a viable solution
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Versatile Porphyrin Arrangements for Photodynamic Therapy—A Review
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Photodynamic Therapy for Inflammatory and Cancerous Diseases of the Intestines: Molecular Mechanisms and Prospects for Application
Deng, B., Wang, K., Zhang, L., Qiu, Z., Dong, W., & Wang, W. (2023) · International Journal of Biological Sciences · doi:10.7150/ijbs.87492 · Cited by 31 · see citing works
Evaluating the photodynamic efficacy of nebulized curcumin-loaded liposomes prepared by thin-film hydration and dual centrifugation: In vitro and in ovo studies
Bender, L., Ayoub, A. M., Schulze, J., Amin, M. U., Librizzi, D., Engelhardt, K. H., Roschenko, V., Yousefi, B. H., Schäfer, J., Preis, E., et al. (2024) · Biomaterials Advances · doi:10.1016/j.bioadv.2024.213823 · Cited by 31 · see citing works
Recent Progress in Thermally Activated Delayed Fluorescence Photosensitizers for Photodynamic Therapy
Li, Z., Lu, J., & Li, X. (2024) · Chemistry - A European Journal · doi:10.1002/chem.202401001 · Cited by 29 · see citing works
From (Sub)Porphyrins to (Sub)Phthalocyanines: Aromaticity Signatures in the UV–Vis Absorption Spectra
Escayola, S., Labella, J., Szczepanik, D. W., Poater, A., Torres⊗, T., Solà, M., & Matito, E. (2024) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.4c03139 · Cited by 29 · see citing works
Phase‐Separated Spiropyran Coacervates as Dual‐Wavelength‐Switchable Reactive Oxygen Generators
Kong, H., Xie, X. N., Bao, Y., Zhang, F., Bian, L., Cheng, K., Zhao, Y., & Xia, J. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202419538 · Cited by 28 · see citing works
Fighting Cancer with Photodynamic Therapy and Nanotechnologies: Current Challenges and Future Directions
Ailioaie, L. M., Ailioaie, C., & Litscher, G. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26072969 · Cited by 28 · see citing works
Recent advancement of nanomedicine-based targeted delivery for cervical cancer treatment
Yadav, R., Das, P. P., Sharma, S., Sengupta, S., Kumar, D., & Sagar, R. (2023) · Medical Oncology · doi:10.1007/s12032-023-02195-3 · Cited by 27 · see citing works
Combining Photodynamic Therapy and Targeted Drug Delivery Systems: Enhancing Mitochondrial Toxicity for Improved Cancer Outcomes
Merlin, J. P. J., Crous, A., & Abrahamse, H. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms251910796 · Cited by 25 · see citing works
Detection and Elimination of Senescent Cells with a Self-Assembled Senescence-Associated β-Galactosidase-Activatable Nanophotosensitizer
Chu, J. C. H., Xiong, J., Wong, C. T. T., Wang, S., Tam, D. Y., García‐Fernández, A., Martínez‐Máñez, R., & Ng, D. K. P. (2023) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.3c01306 · Cited by 26 · see citing works
Current Photodynamic Therapy for Glioma Treatment: An Update
Aebisher, D., Przygórzewska, A., Myśliwiec, A., Dynarowicz, K., Krupka‐Olek, M., Bożek, A., Kawczyk‐Krupka, A., & Bartusik‐Aebisher, D. (2024) · Biomedicines · doi:10.3390/biomedicines12020375 · Cited by 26 · see citing works
Responsive Nanomaterial Delivery Systems for Pancreatic Cancer Management
Elsherbeny, A., Bayraktutan, H., Öz, U. C., Moloney, C., Ashworth, J., Grabowska, A. M., & Alexander, C. (2023) · Advanced Therapeutics · doi:10.1002/adtp.202300330 · Cited by 25 · see citing works
Recent advancements in metal organic framework-modified multifunctional materials for photodynamic therapy
Pattnaik, A. K., Priyadarshini, N., Priyadarshini, P., Behera, G. C., & Parida, K. M. (2024) · Materials Advances · doi:10.1039/d4ma00376d · Cited by 22 · see citing works
Photodynamic Therapy with Targeted Release of Boron-Dipyrromethene Dye from Cobalt(III) Prodrugs in Red Light
Jana, A., Sahoo, S., Paul, S., Sahoo, S., Jayabaskaran, C., & Chakravarty, A. R. (2024) · Inorganic Chemistry · doi:10.1021/acs.inorgchem.4c00244 · Cited by 21 · see citing works
Green synthesis and characterization of AgNPs, liposomal loaded AgNPs and ZnPcS4 photosensitizer for enhanced photodynamic therapy effects in MCF-7 breast cancer cells
Chota, A., Abrahamse, H., & George, B. P. A. (2024) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2024.104252 · Cited by 22 · see citing works
Hybrid Nanoplatforms Based on Photosensitizers and Metal/Covalent Organic Frameworks for Improved Cancer Synergistic Treatment Nano-Delivery Systems
Magadla, A. (2025) · Molecules · doi:10.3390/molecules30040884 · Cited by 18 · see citing works
“Click” for precise photodynamic therapy
Tam, L. K. B., & Ng, D. K. P. (2023) · Materials Chemistry Frontiers · doi:10.1039/d3qm00431g · Cited by 18 · see citing works
Advances in nanotherapeutics for tumor treatment by targeting calcium overload
Wang, C., Peng, J., Xiao, Y., Zhang, Z., Yang, X., Liang, X., Yang, J., Zhou, X., & Li, C. (2024) · Colloids and Surfaces B Biointerfaces · doi:10.1016/j.colsurfb.2024.114190 · Cited by 18 · see citing works
Progress of cell membrane-derived biomimetic nanovesicles for cancer phototherapy
Raza, F., Zafar, H., Jiang, L., Su, J., Yuan, W., Qiu, M., & Paiva‐Santos, A. C. (2023) · Biomaterials Science · doi:10.1039/d3bm01170d · Cited by 17 · see citing works
A Bioorthogonal Antidote Against the Photosensitivity after Photodynamic Therapy
Xue, E. Y., Yang, C., Zhou, Y., & Ng, D. K. P. (2023) · Advanced Science · doi:10.1002/advs.202306207 · Cited by 16 · see citing works
Nanobiohybrid Oncolytic Bacteria with Optimized Intratumoral Distribution for Combined Sono–Photodynamic/Immunotherapy
Zhang, X., Zang, Z., Liang, Z., Xu, X., Zheng, J., Liang, N., Shabiti, S., Wang, Z., Yu, S., Wang, Y., et al. (2025) · ACS Nano · doi:10.1021/acsnano.4c16740 · Cited by 17 · see citing works
A meta-analysis and systematic review of photodynamic therapy for diabetic foot ulcers
Hou, C., Zhang, L., Wang, L., Zhao, S., Nie, J., lv, M., Zhang, W., Su, X., Tian, S., & Li, Y. (2024) · Photodiagnosis and Photodynamic Therapy · doi:10.1016/j.pdpdt.2024.104228 · Cited by 16 · see citing works
Smart nanocarriers for cancer: harnessing exosomes and lipid systems in photodynamic and immunotherapy
Swain, A., Jena, S. R., & Samanta, L. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1687953 · Cited by 15 · see citing works
Nanomaterials in cancer starvation therapy: pioneering advances, therapeutic potential, and clinical challenges
Tran, N. A., Moonshi, S. S., Lam, A. K.-Y., Lu, C. T., Vu, C. Q., Arai, S., & Ta, H. T. (2025) · Cancer and Metastasis Reviews · doi:10.1007/s10555-025-10267-1 · Cited by 16 · see citing works
Photodynamic Therapy and Tumor Microenvironment-Targeting Strategies: A Novel Synergy at the Frontier of Cancer Treatment
Torna, S., Gkretsi, V., & Stylianou, A. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms26178588 · Cited by 14 · see citing works
Engineering iridium(III) complexes for enhancing electron transfer-based photodynamic therapy
Chen, Z., Xue, J., Zhang, T., Lv, W. Y., Hu, X., Xu, Y., & Zhao, Q. (2026) · Coordination Chemistry Reviews · doi:10.1016/j.ccr.2026.217877 · Cited by 14 · see citing works
Umbrella review of photodynamic therapy for cancer: efficacy, safety, and clinical applications
Chen, H., Li, H., Li, H., & Zhang, Z. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2025.1528314 · Cited by 13 · see citing works
Photodynamic therapy-induced inflammation and adverse effects: An updated review
Moloudi, K., Abrahamse, H., & George, B. P. A. (2025) · Biomedical Journal · doi:10.1016/j.bj.2025.100889 · Cited by 11 · see citing works
Recent advances in enhancing the luminescence efficiency of rare earth upconversion nanoparticles for biomedical applications
Guo, C., Ding, Y., Cheng, X., Zhou, T., Xu, Z., Zhang, A. Q., & Shi, F. (2026) · RSC Advances · doi:10.1039/d5ra06977g · Cited by 11 · see citing works
Dual regulation of osteosarcoma hypoxia microenvironment by a bioinspired oxygen nanogenerator for precise single-laser synergistic photodynamic/photothermal/induced antitumor immunity therapy
Zhang, C., Li, D., Zhang, X., Dai, R., Kang, W., Li, Y., Liu, Q., Gao, M., Zheng, Z., Zhang, R., et al. (2024) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101054 · Cited by 11 · see citing works
Application and prospects of nucleic acid nanomaterials in tumor therapy
Lu, W., Chen, T., Xiao, D., Qin, X., Chen, Y., & Shi, S. (2023) · RSC Advances · doi:10.1039/d3ra04081j · Cited by 11 · see citing works
Photodynamic Therapy and Immunological View in Gastrointestinal Tumors
Aebisher, D., Woźnicki, P., Dynarowicz, K., Kawczyk‐Krupka, A., Cieślar, G., & Bartusik‐Aebisher, D. (2023) · Cancers · doi:10.3390/cancers16010066 · Cited by 10 · see citing works
Preparation of GSH-responsive nanoparticles for combined chemo-photothermal therapy codelivering 6-MP and Ce6
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Authors: Huis in ‘t Veld, R. V., Heuts, J., Ma, S., Cruz, L. J., Ossendorp, F. A., & Jager, M. J.
Affiliations: Department of Ophthalmology, Leiden University Medical Centre (LUMC), 2333 ZA Leiden, Zuid-Holland, The Netherlands
Leiden University Medical Center (NL)
ORCID: Heuts, Jeroen
Ma, Sen
Cruz, Luis J.
Ossendorp, Ferry A.
Jager, Martine J.
Venue: Pharmaceutics
Publisher: MDPI AG
Published: 2023-01-18
Volume: 15
Issue: 2
Pages: 330
ISSN: 1999-4923 (ISSN-L)
DOI: 10.3390/pharmaceutics15020330
PMC: PMC9965442
OpenAlex: W4317425740
Cited by: 159
References: 338
Citations by year: 2026: 35 · 2025: 50 · 2024: 48 · 2023: 26
FWCI: 7.36
Type: journal article
Language: en
Open access: gold
doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Pharmaceutics (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Health-Holland (LSHM19061)
Topics: Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
Physical Sciences › Engineering › Biomedical Engineering › Nanoplatforms for cancer theranostics
Health Sciences › Medicine › Epidemiology › Nonmelanoma Skin Cancer Studies
Keywords: photodynamic therapy, cancer therapy, reactive oxygen species, cancer cell death, damage-associated molecular patterns, antitumor immunity, immunotherapy

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