非凋亡铁死亡是一种有前途的癌症治疗方法，它为传统凋亡诱导的程序性癌细胞死亡疗法的多药耐药性提供了解决方案。减少细胞内谷胱甘肽 (GSH) 对于诱导过量 ROS 至关重要，并且被认为是引发铁死亡的关键过程。然而，由于目标有限，单独减少 GSH 的治疗并未产生令人满意的效果。在这方面，构建了具有双重 GSH 消耗能力的 FeCD（Fe3 修饰的 L-组氨酸来源的碳点），通过自我放大瘤内氧化应激来工程铁死亡。碳点具有消耗GSH的能力，Fe3的引入可以放大CDs的GSH消耗能力，与肿瘤微环境中过量的H2O2反应生成高度氧化的•OH。这是一种通过将 Fe3 和 CD 与 GSH 消耗活性相结合的协同自我放大疗法的新策略。通过以水包油的方式封装FeCDs制备酸触发降解材料(FeCDs@PAE-PEG)。与其他引发铁死亡的纳米粒子相比，所建立的FeCDs@PAE-PEG具有靶向性，在无需红外光和超声波参与的情况下，显着提高了GSH的消耗效率和过量铁的积累。这种协同策略在体外和体内均表现出优异的铁死亡诱导能力和抗肿瘤功效，为铁死亡的临床转化提供了巨大的潜力。

Nonapoptotic ferroptosis is a promising cancer treatment which offers a solution to the multidrug resistance of conventional apoptosis-induced programmed cancer cell death therapies. Reducing intracellular glutathione (GSH) is essential for inducing excess ROS and has been considered a crucial process to trigger ferroptosis. However, treatments reducing GSH alone have not produced satisfactory effects due to their restricted target. In this regard, FeCDs (Fe3+-modified l-histidine -sourced carbon dots) with dual GSH-consumption capabilities were constructed to engineer ferroptosis by self-amplifying intratumoral oxidative stress. Carbon dots have the ability to consume GSH, and the introduction of Fe3+ can amplify the GSH-consuming ability of CDs, reacting with excess H2O2 in the tumor microenvironment to generate highly oxidized •OH. This is a novel strategy through synergistic self-amplification therapy combining Fe3+ and CDs with GSH-consuming activity. The acid-triggered degradation material (FeCDs@PAE-PEG) was prepared by encapsulating FeCDs in an oil-in-water manner. Compared with other ferroptosis-triggering nanoparticles, the established FeCDs@PAE-PEG is targeted and significantly enhances the consumption efficiency of GSH and accumulation of excess iron without the involvement of infrared light and ultrasound. This synergistic strategy exhibits excellent ferroptosis-inducing ability and antitumor efficacy both in vitro and in vivo and offers great potential for clinical translation of ferroptosis.