Experimental investigation of a combinational iron chelating protoporphyrin IX prodrug for fluorescence detection and photodynamic therapy
dc.contributor.author | Magnussen, A | |
dc.contributor.author | Reburn, C | |
dc.contributor.author | Perry, A | |
dc.contributor.author | Wood, M | |
dc.contributor.author | Curnow, A | |
dc.date.accessioned | 2021-07-05T10:06:39Z | |
dc.date.issued | 2021-07-04 | |
dc.description.abstract | Photodynamic therapy (PDT) is an oxygen-dependent, light-activated, and locally destructive drug treatment of cancer. Protoporphyrin IX (PpIX)-induced PDT exploits cancer cells’ own innate heme biosynthesis to hyper-accumulate the naturally fluorescent and photoactive precursor to heme, PpIX. This occurs as a result of administering heme precursors (e.g., aminolevulinic acid; ALA) because the final step of the pathway (the insertion of ferrous iron into PpIX by ferrochelatase to form heme) is relatively slow. Separate administration of an iron chelating agent has previously been demonstrated to significantly improve dermatological PpIX-PDT by further limiting heme production. A newly synthesized combinational iron chelating PpIX prodrug (AP2-18) has been assessed experimentally in cultured primary human cells of bladder and dermatological origin, as an alternative photosensitizing agent to ALA or its methyl or hexyl esters (MAL and HAL respectively) for photodetection/PDT. Findings indicated that the technique of iron chelation (either through the separate administration of the established hydroxypyridinone iron chelator CP94 or the just as effective combined AP2-18) did not enhance either PpIX fluorescence or PDT-induced (neutral red assessed) cell death in human primary normal and malignant bladder cells. However, 500 µM AP2-18 significantly increased PpIX accumulation and produced a trend of increased cell death within epithelial squamous carcinoma cells. PpIX accumulation destabilized the actin cytoskeleton in bladder cancer cells prior to PDT and resulted in caspase-3 cleavage/early apoptosis afterwards. AP2-18 iron chelation should continue to be investigated for the enhancement of dermatological PpIX-PDT applications but not bladder photodetection/PDT. | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.description.sponsorship | Killing Cancer | en_GB |
dc.identifier.citation | Published online 4 July 2021 | en_GB |
dc.identifier.doi | 10.1007/s10103-021-03367-1 | |
dc.identifier.uri | http://hdl.handle.net/10871/126295 | |
dc.language.iso | en | en_GB |
dc.publisher | Springer | en_GB |
dc.rights | © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. . | en_GB |
dc.subject | Fluorescence | en_GB |
dc.subject | Iron chelation | en_GB |
dc.subject | Iron chelating agent | en_GB |
dc.subject | Photodetection | en_GB |
dc.subject | Photodynamic therapy (PDT) | en_GB |
dc.subject | Protoporphyrin IX (PpIX) | en_GB |
dc.title | Experimental investigation of a combinational iron chelating protoporphyrin IX prodrug for fluorescence detection and photodynamic therapy | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2021-07-05T10:06:39Z | |
dc.identifier.issn | 0268-8921 | |
dc.description | This is the final version. Available on open access from Springer via the DOI in this record | en_GB |
dc.identifier.journal | Lasers in Medical Science | en_GB |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2021-06-21 | |
exeter.funder | ::Duchy Health Charity Trust | en_GB |
exeter.funder | ::Medical Research Council (MRC) | en_GB |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2021-07-04 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2021-07-05T08:45:07Z | |
refterms.versionFCD | AM | |
refterms.dateFOA | 2021-07-05T10:06:56Z | |
refterms.panel | A | en_GB |
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Except where otherwise noted, this item's licence is described as © The Author(s) 2021. Open Access. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
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