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Conventional treatments include cytoreductive surgery followed by multi\u2010line platinum and taxane chemotherapy regimens. Despite an initial response to treatment, over 75% of patients with advanced\u2010stage ovarian cancer will relapse and succumb to platinum\u2010resistant disease. Recent evidence suggests that fluid shear stress (FSS), which results from the movement of fluid such as ascites, induces epithelial\u2010to\u2010mesenchymal transition and confers resistance to carboplatin in ovarian cancer cells. This study demonstrates, for the first time, that FSS\u2010induced platinum resistance correlates with increased cellular protoporphyrin IX (PpIX), the penultimate downstream product of heme biosynthesis, the production of which can be enhanced using the clinically approved pro\u2010drug aminolevulinic acid (ALA). These data suggest that, with further investigation, PpIX could serve as a fluorescence\u2010based biomarker of FSS\u2010induced platinum resistance. Additionally, this study investigates the efficacy of PpIX\u2010enabled photodynamic therapy (PDT) and the secretion of extracellular vesicles under static and FSS conditions in Caov\u20103 and NIH:OVCAR\u20103 cells, two representative cell lines for high\u2010grade serous ovarian carcinoma (HGSOC), the most lethal form of the disease. FSS induces resistance to ALA\u2010PpIX\u2010mediated PDT, along with a significant increase in the number of EVs. Finally, the ability of PpIX\u2010mediated photodynamic priming (PDP) to enhance carboplatin efficacy under FSS conditions is quantified. These preliminary findings in monolayer cultures necessitate additional studies to determine the feasibility of PpIX as a fluorescence\u2010based indicator, and mediator of PDP, to target chemoresistance in the context of FSS.<\/jats:p>","DOI":"10.1111\/php.14014","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T10:55:30Z","timestamp":1724756130000},"page":"1603-1621","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>PpIX<\/scp>\u2010enabled fluorescence\u2010based detection and photodynamic priming of platinum\u2010resistant ovarian cancer cells under fluid shear stress"],"prefix":"10.1111","volume":"100","author":[{"given":"Mustafa Kemal","family":"Ruhi","sequence":"first","affiliation":[{"name":"Joint Department of Biomedical Engineering University of North Carolina at Chapel Hill and North Carolina State University  Chapel Hill North Carolina USA"},{"name":"Institute of 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