Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro
dc.contributor.author | Reburn, C | |
dc.contributor.author | Gawthorpe, G | |
dc.contributor.author | Perry, A | |
dc.contributor.author | Wood, M | |
dc.contributor.author | Curnow, A | |
dc.date.accessioned | 2023-11-27T11:37:43Z | |
dc.date.issued | 2023-11-24 | |
dc.date.updated | 2023-11-27T10:38:57Z | |
dc.description.abstract | (1) Background: The protoporphyrin IX (PpIX)-mediated fluorescence-guided resection and interoperative photodynamic therapy (PDT) of remaining cells may be effective adjuvants to the resection of glioma. Both processes may be enhanced by increasing intracellular PpIX concentrations, which can be achieved through iron chelation. AP2-18 is a novel combinational drug, which ester-links a PpIX precursor (aminolaevulinic acid; ALA) to an iron-chelating agent (CP94). (2) Methods: Human glioma U-87 MG cells were cultured in 96-well plates for 24 h and incubated for 3 or 6 h with various test compound combinations: ALA (±) CP94, methyl aminolevulinate (MAL) (±) CP94 and AP2-18. PpIX fluorescence was measured at 0, 3 or 6 h with a Bio-tek Synergy HT plate reader, as well as immediately after irradiation with a 635 nm red light (Aktilite CL16 LED array), representing the PDT procedure. Cell viability post-irradiation was assessed using the neutral red assay. (3) Results: AP2-18 significantly increased PpIX fluorescence compared to all other test compounds. All treatment protocols effectively achieved PDT-induced cytotoxicity, with no significant difference between test compound combinations. (4) Conclusions: AP2-18 has potential to improve the efficacy of fluorescence-guided resection either with or without the subsequent intraoperative PDT of glioma. Future work should feature a more complex in vitro model of the glioma microenvironment. | en_GB |
dc.description.sponsorship | Killing Cancer | en_GB |
dc.description.sponsorship | Medical Research Council (MRC) | en_GB |
dc.format.extent | 2668-2668 | |
dc.identifier.citation | Vol. 15(12), article 2668 | en_GB |
dc.identifier.doi | https://doi.org/10.3390/pharmaceutics15122668 | |
dc.identifier.uri | http://hdl.handle.net/10871/134664 | |
dc.identifier | ORCID: 0000-0003-1616-4790 (Curnow, Alison) | |
dc.identifier | ScopusID: 7004272076 (Curnow, Alison) | |
dc.language.iso | en | en_GB |
dc.publisher | MDPI | en_GB |
dc.rights | © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). | en_GB |
dc.subject | fluorescence-guided resection (FGR) | en_GB |
dc.subject | photodynamic therapy (PDT) | en_GB |
dc.subject | iron chelation | en_GB |
dc.subject | protoporphyrin IX (PpIX) | en_GB |
dc.subject | glioma | en_GB |
dc.subject | AP2-18 | en_GB |
dc.subject | aminolaevulinic acid (ALA) | en_GB |
dc.subject | MAL | en_GB |
dc.title | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro | en_GB |
dc.type | Article | en_GB |
dc.date.available | 2023-11-27T11:37:43Z | |
dc.description | This is the final version. Available on open access from MDPI via the DOI in this record | en_GB |
dc.description | Data Availability Statement: The data can be shared on request. | en_GB |
dc.identifier.eissn | 1999-4923 | |
dc.identifier.journal | Pharmaceutics | en_GB |
dc.relation.ispartof | Pharmaceutics, 15(12) | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0/ | en_GB |
dcterms.dateAccepted | 2023-11-20 | |
rioxxterms.version | VoR | en_GB |
rioxxterms.licenseref.startdate | 2023-11-24 | |
rioxxterms.type | Journal Article/Review | en_GB |
refterms.dateFCD | 2023-11-27T11:36:06Z | |
refterms.versionFCD | VoR | |
refterms.dateFOA | 2023-11-27T11:37:51Z | |
refterms.panel | A | en_GB |
refterms.dateFirstOnline | 2023-11-24 |
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Except where otherwise noted, this item's licence is described as © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).