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Harnessing the UVA-Induced Redox Active Labile Iron Release to Improve the Efficiency of 5-Aminolevulinic Acid-Based Photodynamic Therapy (ALA-PDT) of Skin Cancer

Charareh Pourzand

Prof. Charareh Pourzand from the University of Bath, United Kingdom will join this year's congress and give a talk on "Harnessing the UVA-Induced Redox Active Labile Iron Release to Improve the Efficiency of 5-Aminolevulinic Acid-Based Photodynamic Therapy (ALA-PDT) of Skin Cancer".

Topical ALA-PDT of skin cancer is based on ALA-mediated accumulation of protoporphyrin IX (PpIX), which upon exposure to high-intensity visible light, can catalyze the generation of ROS, resulting in cell death.


However, to improve the efficiency of ALA-PDT, she used UVA as the light source to decrease considerably the duration of phototherapy, as UVA is absorbed more efficiently by PpIX and is significantly more cytotoxic than conventional lights.
Furthermore UVA can increase the intracellular levels of harmful labile iron (LI),which in turn is a major contributor to cell death by acting as a catalyst for oxidative cell damage.


Prof. Pourzand adopted both indoor and outdoor UVA-based light fractionation ALA-PDT protocol as her optimization strategy, using HaCaT keratinocytes as a model. The cytotoxicity MTT and clone forming assays corroborated with spectrofluorimeter-based measurements of ALA-mediated PpIX accumulation and UVA-mediated LI release.


As for the results, exploiting the rapid release of LI following application of short pulses of low UVA doses (1-2.5 kJ/m2) to ALA-treated cells rather than a continuous visible light source, sensitized HaCaT cells to subsequent UVA doses leading to maximum photo-killing. In conclusion, this study highlights the potential of UVA-based light fractionation to improve the topical ALA-PDT protocols for actinic keratosis and superficial non-melanoma skin cancer.

Paris Redox 2021 Congress
October 13-15, 2021 - Interactive Online Congress
www.isanh.net

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