Abstract

Ferroptosis is a novel type of nonapoptotic cell death, showing a hopeful potential in cancer therapeutic schedules. Oneof the apparent features of ferroptosis is the lipid hydroperoxides producing ROS induced by intracellular iron ionsaccumulation. Thus the iron regulation and metabolism in the cell is an essential factors for the trigger of ferroptosis.We designed a new nanoparticle that loaded ferric ions and siamese based on polydopamine nanomaterial (siramesine@Fe(III) PDA NPs) to induce breast cancer ferroptosis through the Fenton reaction. Iron ions can be added to cancer cells,and siamese can block the exportation of intracellular iron by inhibiting the expression of FPN, thus promoting theFenton reaction. The extra transport of iron ions into cells by nanoparticles and the inhibition of iron ions outward bySiramesine promoted the accumulation of iron ions in cells, thus achieving a synergistic effect leading to ferroptosis incells. In addition, NPs demonstrated excellent pH-responsive degradation, with enhanced drug release at the pH valueof tumor microenvironments and lysosomal. Siramesine@Fe(III) PDA NPs showed good ferroptosis induction ability,displaying the potential for cancer treatment.

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