@article{Zhang2025, 
author = {Limei Zhang and Huatai Zhu and Yuting Ren and Peng Ye and Jiandu Lei},
title = {Ferrocene conjugated glutathione consumption for enhanced ferroptosis therapy and chemotherapy},
year = {2025},
journal = {Nano Research},
volume = {18},
number = {4},
pages = {94907298},
keywords = {ferroptosis, glutathione consumption, ferrocene (Fc), honokiol (HNK), hydroxycamptothecin (HCPT)},
url = {https://www.sciopen.com/article/10.26599/NR.2025.94907298},
doi = {10.26599/NR.2025.94907298},
abstract = {As the backbone of tumor therapy, chemotherapy is prone to tumor resistance due to its apoptotic pathway. Ferroptosis, as an effective form of non-apoptotic cell death, can overcome chemotherapy apoptosis-induced resistance. Therefore, the combination of chemotherapy and ferroptosis is a highly promising tumor treatment strategy. However, high glutathione (GSH) and insufficient intracellular iron content in the tumor environment limit the efficiency of ferroptosis-mediated anticancer. Not only that, simultaneous intracellular delivery of iron sources, ferroptosis inducers, and chemotherapeutic agents remains a major challenge. Here, we constructed a self-assembled nano prodrug system to co-deliver iron sources, ferroptosis inducers, and anti-cancer drugs for combined ferroptosis and chemotherapy. In the tumor microenvironment, high levels of GSH triggered redox-responsive disulfide bonding, which induced the disassembly of this nano prodrug system (PFSH@HCPT), releasing hydroxycamptothecin (HCPT), honokiol (HNK) and ferrocene (Fc). HCPT induced cell death via apoptosis and Fc triggered the Fenton reaction, which induced ferroptosis. HNK inhibited the activity of glutathione peroxidase 4 (GPX4) to enhance ferroptosis, and on the other hand, it further induced cell death via apoptosis. Meanwhile, the combined strategy of HNK-mediated resistance and ferroptosis-induced resistance mechanism further overcame the resistance of HCPT and significantly improved the therapeutic efficacy. This nano prodrug system realized the “multi-machine integrated” therapeutic efficacy and showed great therapeutic potential, which may open up a new way for effective cancer treatment.}
}