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Pancreatic Ductal Adenocarcinoma (PDAC) is a very aggressive disease, lacking effective therapeutic approaches and leaving PDAC patients with a poor prognosis. The life expectancy of PDAC patients has not experienced a significant change in the last few decades with a five-year survival rate of only 8%. To address this unmet need, novel pharmacological targets must be identified for clinical inter

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Lipid nanoparticles (LNPs) are clinically approved for mRNA-based vaccines and liver-targeted siRNA delivery. However, poor nucleic acid delivery efficiency limits their application in extrahepatic tissues and tumors. Here, using live-cell and super-resolution microscopy, we identify multiple distinct steps of inefficiencies in the cytosolic delivery of both siRNA and mRNA cargoes. Membrane damage