State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Public Health, Shenzhen Research Institute of Xiamen University, Xiamen University, Xiamen, 361102, China.
Department of Rheumatology and Immunology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Adv Sci (Weinh). 2024 Oct;11(39):e2403305. doi: 10.1002/advs.202403305. Epub 2024 Aug 19.
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--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.
铁死亡被认为介导了化疗药物诱导的急性肾损伤（AKI）的发病机制；然而，利用基于铁死亡的治疗方法来进行肾脏保护仍然具有挑战性。在这里，设计了超小纳米点，称为 FerroD，由两亲性缀合物（四苯乙烯-丝氨酸-去铁胺，TPE-lys-Ser-DFO（TSD））和包裹的 ferrostatin-1 组成。通过肾损伤分子-1 介导的内吞作用内化后，FerroD 可以通过配位-解组装机制同时去除过载的铁离子并消除脂质过氧化物的过度产生，这共同赋予了铁死亡的显著抑制效率。在顺铂（CDDP）诱导的 AKI 小鼠中，具有双重抗铁死亡能力的 FerroD 可以提供长期的肾脏保护作用。这项研究可能为针对各种与铁死亡相关的肾脏疾病的铁死亡靶向治疗的设计和临床转化提供新的思路。
