Ultrasmall Nanodots with Dual Anti‐Ferropototic Effect for Acute Kidney Injury Therapy

Abstract Ferroptosis is known to mediate the pathogenesis of chemotherapeutic drug‐induced acute kidney injury (AKI); however, leveraging the benefits of ferroptosis‐based treatments for nephroprotection remains challenging. Here, ultrasmall nanodots, denoted as FerroD, comprising the amphiphilic conjugate (tetraphenylethylene‐ L ‐serine‐deferoxamine, TPE‐lys‐Ser‐DFO (TSD)) and entrapped ferrostatin‐1 are designed. After being internalized through kidney injury molecule‐1‐mediated endocytosis, FerroD can simultaneously remove the overloaded iron ions and eliminate the overproduction of lipid peroxides by the coordination‐disassembly mechanisms, which collectively confer prominent inhibition efficiency of ferroptosis. In cisplatin (CDDP)‐induced AKI mice, FerroD equipped with dual anti‐ferroptotic ability can provide long‐term nephroprotective effects. This study may shed new light on the design and clinical translation of therapeutics targeting ferroptosis for various ferroptosis‐related kidney diseases.