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A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy.

ABSTRACT: Photodynamic Therapy (PDT) using Aminolevulinic acid (ALA) could be an effective and minimally invasively applicable way to treat many different types of tumors without radiation and large incisions by just applying a light pulse. However the PDT process is difficult to observe, control and optimize and the dynamical relationships between the variables involved in the process is complex and still hardly understood. One of the main variables affecting the outcome of the process is the determination of the interval of time between ALA inoculation and starting of light delivery. This interval, better known as drug-light interval, should ensure that enough Protoporphyrin IX (PPIX) is located in the vicinity of functional structures inside the cells for the greatest damage during the PDT procedure. One route to better estimate this time interval would be by predicting PPIX from the dynamical changes of its precursors. For that purpose, in this work a novel optical setup (OS) is proposed for differentiating fluorescence emitted by Coproporphyrin III (CPIII) and PPIX itself in samples composed of mixed solutions. The OS is tested using samples with different concentrations in mixed solutions of PPIX and the precursor CPIII as well as with a Polymethyl methacrylate test sample as additional reference. Results show that emitted fluorescence of the whole process can be measured independently for PPIX and its precursor, which can enable future developments on PPIX prediction from the dynamical changes of its precursor for subject-dependent drug-light interval assessment.

SUBMITTER: Landes R

PROVIDER: S-EPMC6118380 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy.

Landes Rainer R Illanes Alfredo A Goeppner Daniela D Gollnick Harald H Friebe Michael M

PloS one 20180831 8

Photodynamic Therapy (PDT) using Aminolevulinic acid (ALA) could be an effective and minimally invasively applicable way to treat many different types of tumors without radiation and large incisions by just applying a light pulse. However the PDT process is difficult to observe, control and optimize and the dynamical relationships between the variables involved in the process is complex and still hardly understood. One of the main variables affecting the outcome of the process is the determinati ...[more]

PMID: 30169536

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Project description:ObjectivesNon-melanoma skin cancers are the most frequently occurring type of cancer worldwide. They can be effectively treated using topical dermatological photodynamic therapy (PDT) employing protoporphyrin IX (PpIX) as the active photosensitising agent as long as the disease remains superficial. Novel iron chelating agents are being investigated to enhance the effectiveness and extend the applications of this treatment modality, as limiting free iron increases the accumulation of PpIX available for light activation and thus cell kill.MethodsHuman lung fibroblasts (MRC-5) and epithelial squamous carcinoma (A431) cells were treated with PpIX precursors (aminolaevulinic acid [ALA] or methyl-aminolevulinate [MAL]) with or without the separate hydroxypyridinone iron chelating agent (CP94) or alternatively, the new combined iron chelator and PpIX producing agent, AP2-18. PpIX fluorescence was monitored hourly for 6 hours prior to irradiation. PDT effectiveness was then assessed the following day using the lactate dehydrogenase and neutral red assays.ResultsGenerally, iron chelation achieved via CP94 or AP2-18 administration significantly increased PpIX fluorescence. ALA was more effective as a PpIX-prodrug than MAL in A431 cells, corresponding with the lower PpIX accumulation observed with the latter congener in this cell type. Addition of either iron chelating agent consistently increased PpIX accumulation but did not always convey an extra beneficial effect on PpIX-PDT cell kill when using the already highly effective higher dose of ALA. However, these adjuvants were highly beneficial in the skin cancer cells when compared with MAL administration alone. AP2-18 was also at least as effective as CP94 + ALA/MAL co-administration throughout and significantly better than CP94 supplementation at increasing PpIX fluorescence in MRC5 cells as well as at lower doses where PpIX accumulation was observed to be more limited.ConclusionsPpIX fluorescence levels, as well as PDT cell kill effects on irradiation can be significantly increased by pyridinone iron chelation, either via the addition of CP94 to the administration of a PpIX precursor or alternatively via the newly synthesized combined PpIX prodrug and siderophore, AP2-18. The effect of the latter compound appears to be at least equivalent to, if not better than, the separate administration of its constituent parts, particularly when employing MAL to destroy skin cancer cells. AP2-18 therefore warrants further detailed analysis, as it may have the potential to improve dermatological PDT outcomes in applications currently requiring enhancement. Lasers Surg. Med. 50:552-565, 2018. © 2018 The Authors. Lasers in Surgery and Medicine Published by Wiley Periodicals, Inc.

Dataset Information

A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy.

Publications

A study of concentration changes of Protoporphyrin IX and Coproporphyrin III in mixed samples mimicking conditions inside cancer cells for Photodynamic Therapy.

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