Administration of 5-aminolevulinic acid (ALA) as a precursor for protoporphyrin IX (PpIX) is an established photosensitization strategy for photodynamic therapy (PDT) and fluorescence guided surgery. Ongoing studies seek to identify strategies to enhance PpIX accumulation as well as phenotypic traits that correlate with high PpIX conversion. Here we examine PpIX accumulation, PDT response, and differential gene expression in pancreatic and oral cancer cells compared to derivative sublines with acquired drug resistance. The latter exhibit poor differentiation and increased EMT but marked increase in PpIX conversion and enhanced response to PDT. RNAseq analysis shows dramatic changes in expression of genes relevant to PpIX transport (ABCG2) and PpIX formation (ALAD).
Photodynamic therapy (PDT) is a light-based modality that shows promise for adaptation and implementation as a cancer treatment technology in resource-limited settings. In this context PDT is particularly well suited for treatment of pre-cancer and early stage malignancy of the oral cavity, that present a major global health challenge, but for which light delivery can be achieved without major infrastructure requirements. In recent reports we demonstrated that a prototype low-cost batterypowered 635nm LED light source for ALA-PpIX PDT achieves tumoricidal efficacy in vitro and vivo, comparable to a commercial turn-key laser source. Here, building on these reports, we describe the further development of a prototype PDT device to enable intraoral light delivery, designed for ALA- PDT treatment of precancerous and cancerous lesions of the oral cavity. We evaluate light delivery via fiber bundles and customized 3D printed light applicators for flexible delivery to lesions of varying size and position within the oral cavity. We also briefly address performance requirements (output power, stability, and light delivery) and present validation of the device for ALA-PDT treatment in monolayer squamous carcinoma cell cultures.
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