Experimental findings utilising a new iron chelating ALA prodrug to enhance protoporphyrin IX-induced photodynamic therapy

Reburn, Charlotte; Anayo, Lizette; Magnussen, Anette; Perry, Alexis; Wood, Mark E.; Curnow, Alison

doi:10.1117/12.2525819

Cited by 2 publications

(2 citation statements)

References 17 publications

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“…Therefore, iron chelation represents an attractive target that can enhance the efficacy of ALA-PDT. Reburn et al synthesized an ester between ALA and the hydroxypyridinone iron chelating agent CP94 and observed significant enhanced effects on both PpIX accumulation and PDT cytotoxicity in glioma cells [39]. Also, coincubation of CP94 with ALA, methyl aminolevulinate (MAL) and hexyl aminolevulinate (HAL) increased PpIX accumulation.…”

Section: Ferrochelatasementioning

confidence: 99%

Molecular Insights into Photodynamic Therapy of Glioma

Aebisher,

Woźnicki,

Bartusik-Aebisher

2024

Preprint

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Cancers, a large and heterogeneous group of malignancies, are becoming an increasingly important cause of premature mortality worldwide. 2% of these are primary CNS tumors, of which 24% are gliomas. These tumors are diverse, but what they have in common is one of the most unfavorable prognoses among all cancers. A patient's future varies depending on the grade of the diagnosed glioma. To date, however, no standard treatment for grade IV has been established. All glioblastomas eventually undergo progression or recurrence. The current standard of treatment, which includes surgical intervention, radiation therapy and chemotherapy, is therefore far from sufficient. Work is constantly underway to discover a new, effective form of glioma therapy. Photodynamic therapy (PDT) may be one of them. It involves the local or systemic application of a photosensitive compound - a photosensitizer (PS), which accumulates in the affected tissues. Photosensitizer molecules absorb light of the appropriate wavelength, initiating activation processes leading to the formation of reactive oxygen species and selective destruction of inappropriate cells. Currently, this method has been approved for the treatment of several cancers. Research focusing on the effective use of PDT in glioma therapy is already underway, with promising results. In our work, we present molecular insights into PDT of glioma. Based on the available literature, we analyze and systematize the impact of various molecules, proteins, transporters and transmitters on the efficacy of PDT and the effect of PDT on their expression. In addition, we highlight gaps in current knowledge and point out directions for future research that may contribute to the efficacy of PDT glioma.

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Section: Ferrochelatasementioning

confidence: 99%

Molecular Insights into Photodynamic Therapy of Glioma

Aebisher,

Woźnicki,

Bartusik-Aebisher

2024

Preprint

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“…The novel drug AP2-18 (synthesised by the University of Exeter) consists of the PpIX precursor ALA ester-linked to the iron chelator CP94 [Patent Application WO2014033477A1; 6 March 2014 [ 21 ]]. This highly soluble prodrug facilitates the simultaneous co-delivery of the two components in equimolar amounts.…”

Section: Introductionmentioning

confidence: 99%

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro

Reburn,

Gawthorpe,

Perry

et al. 2023

Pharmaceutics

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(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.

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Experimental findings utilising a new iron chelating ALA prodrug to enhance protoporphyrin IX-induced photodynamic therapy

Cited by 2 publications

References 17 publications

Molecular Insights into Photodynamic Therapy of Glioma

Molecular Insights into Photodynamic Therapy of Glioma

Novel Iron-Chelating Prodrug Significantly Enhanced Fluorescence-Mediated Detection of Glioma Cells Experimentally In Vitro

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