Improving in vitro photodynamic therapy through the development of a novel iron chelating aminolaevulinic acid prodrug
Open accessAbstract
BACKGROUND: Photodynamic therapy (PDT) is a light activated drug therapy that can be used to treat a number of cancers and precancers. It is particularly useful in its topical form in dermatology but improvement of efficacy is required to widen its application. METHODS: An ester between aminolaevulinic acid (ALA) and CP94 was synthesised (AP2-18) and experimentally evaluated to determine whether protoporphyrin IX (PpIX)-induced PDT effectiveness could be improved. A biological evaluation of AP2-18 was conducted in cultured human primary cells with both PpIX fluorescence and cell viability (as determined via the neutral red assay) being assessed in comparison to the PpIX prodrugs normally utilised in clinical practice (aminolaevulinic acid (ALA) or its methyl ester (MAL)) either administered alone or with the comparator iron chelator, CP94. RESULTS: No significant dark toxicity was observed in human lung fibroblasts but AP2-18 significantly increased PpIX accumulation above and beyond that achieved with ALA or MAL administration +/- CP94 in both human dermal fibroblasts and epithelial squamous carcinoma cells. On light exposure, the combined hydroxypyridinone iron chelating ALA prodrug AP2-18 generated significantly greater cytotoxicity than any of the other treatment parameters investigated when the lowest concentration (250 μM) was employed. CONCLUSIONS: Newly synthesised AP2-18 is therefore concluded to be an efficacious prodrug for PpIX-induced PDT in these dermatologically relevant human cells, achieving enhanced effects at lower concentrations than currently possible with existing pharmaceuticals.
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Multiple studies indicate that AP2-18 increases ALA-PpIX fluorescence and PDT as effectively as ALA and CP94 co-administered separately.
“Multiple studies with different cell lines indicate that AP2-18 increases ALA-PpIX fluorescence and PDT as effectively as ALA and CP94 co-administered separately [99,100,101].”
From 5-Aminolevulinic Acid as a Theranostic Agent for Tumor Fluorescence Imaging and Photodynamic Therapy (2023) · cites this paper as [100]
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Jiang, X., Feng, M., Niu, X., Wang, S. H., Sun, Y., Chen, W., & Bai, R. (2026) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2026.2700840
BindingDB (2022) · UC San Diego · doi:10.7270/q28p646m
- Authors
- Curnow, A., Perry, A., & Wood, M.
- Affiliations
- University of Exeter (GB)
- Corresponding author
- Curnow, Alison
- Venue
- Photodiagnosis and Photodynamic Therapy
- Publisher
- Elsevier BV
- Published
- 2019-03
- Volume
- 25
- Pages
- 157-165
- ISSN
- 1572-1000 (ISSN-L)
- PMC
- PMC6456724
- OpenAlex
- W2904634565
- Cited by
- 22
- References
- 82
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 3 · 2020: 5 · 2019: 3
- FWCI
- 2.07
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Photodiagnosis and Photodynamic Therapy (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Figshare (submittedVersion, cc-by)
- Open Research Exeter (University of Exeter) (submittedVersion, cc-by)
- Funders
- Proximity to Discovery grant from the Medical Research Council, UK
- Killing Cancer, UK
- Topics
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Photodynamic Therapy Research Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Porphyrin Metabolism and Disorders
- Physical Sciences › Materials Science › Materials Chemistry › Porphyrin and Phthalocyanine Chemistry
- Keywords
- photodynamic therapy, iron chelation, protoporphyrin IX, hydroxypyridinone, topical photodynamic therapy, dermal fibroblasts, cytotoxicity, dark toxicity
- MeSH terms
- Aminolevulinic Acid, Cell Survival, Humans, Iron Chelating Agents, Photochemotherapy, Prodrugs, Protoporphyrins, Pyridones, Skin Neoplasms, Photosensitizing Agents, Cell Line, Tumor
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