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Thus, ferrous iron is a critical mediator in the pathophysiology of APAP-induced cell death through its uptake into mitochondria, which promotes the injury process by facilitating protein nitration, not by supporting Fenton reaction and lipid peroxidation under normal conditions

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[0803] Enhanced Delivery: As used herein, the term“enhanced delivery” means delivery of more (e.g., at least 1.5 fold more, at least 2-fold more, at least 3-fold more, at least 4-fold more, at least 5-fold more, at least 6-fold more, at least 7-fold more, at least 8-fold more, at least 9-fold more, at least 10-fold more) of a polynucleotide by a nanoparticle to a target tissue of interest (e.g., mammalian liver) compared to the level of delivery of a polynucleotide by a control nanoparticle to a target tissue of interest (e.g., MC3, KC2, or DLinDMA)