Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro
(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 ach...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-11-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/12/2668 |
| _version_ | 1827573827954016256 |
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| author | Charlotte Reburn George Gawthorpe Alexis Perry Mark Wood Alison Curnow |
| author_facet | Charlotte Reburn George Gawthorpe Alexis Perry Mark Wood Alison Curnow |
| author_sort | Charlotte Reburn |
| collection | DOAJ |
| description | (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. |
| first_indexed | 2024-03-08T20:26:42Z |
| format | Article |
| id | doaj.art-1d2a1db292d64b909ae03656136a9245 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T20:26:42Z |
| publishDate | 2023-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-1d2a1db292d64b909ae03656136a92452023-12-22T14:31:54ZengMDPI AGPharmaceutics1999-49232023-11-011512266810.3390/pharmaceutics15122668Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In VitroCharlotte Reburn0George Gawthorpe1Alexis Perry2Mark Wood3Alison Curnow4Knowledge Spa, Royal Cornwall Hospital, University of Exeter, Truro TR1 3HD, UKKnowledge Spa, Royal Cornwall Hospital, University of Exeter, Truro TR1 3HD, UKKnowledge Spa, Royal Cornwall Hospital, University of Exeter, Truro TR1 3HD, UKKnowledge Spa, Royal Cornwall Hospital, University of Exeter, Truro TR1 3HD, UKKnowledge Spa, Royal Cornwall Hospital, University of Exeter, Truro TR1 3HD, UK(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.https://www.mdpi.com/1999-4923/15/12/2668fluorescence-guided resection (FGR)photodynamic therapy (PDT)iron chelationprotoporphyrin IX (PpIX)gliomaAP2-18 |
| spellingShingle | Charlotte Reburn George Gawthorpe Alexis Perry Mark Wood Alison Curnow Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro Pharmaceutics fluorescence-guided resection (FGR) photodynamic therapy (PDT) iron chelation protoporphyrin IX (PpIX) glioma AP2-18 |
| title | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro |
| title_full | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro |
| title_fullStr | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro |
| title_full_unstemmed | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro |
| title_short | Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro |
| title_sort | novel iron chelating prodrug significantly enhanced fluorescence mediated detection of glioma cells experimentally in vitro |
| topic | fluorescence-guided resection (FGR) photodynamic therapy (PDT) iron chelation protoporphyrin IX (PpIX) glioma AP2-18 |
| url | https://www.mdpi.com/1999-4923/15/12/2668 |
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