Functionalized Fe-Doped Carbon Dots Exhibiting Dual Glutathione Consumption to Amplify Ferroptosis for Enhanced Cancer Therapy
Mingyue Zhou, Ziwei Yang, Tianpeng Yin, Yunfeng Zhao, Cai-Yun Wang, Guo‐Yuan Zhu, Li‐Ping Bai, Zhi‐Hong Jiang, Wei Zhang
Abstract
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 (Fe 3+ -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 Fe 3+ can amplify the GSH-consuming ability of CDs, reacting with excess H 2 O 2 in the tumor microenvironment to generate highly oxidized • OH. This is a novel strategy through synergistic self-amplification therapy combining Fe 3+ 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.