Advances in Ferroptosis-Inducing Agents by Targeted Delivery System in Cancer Therapy

Debiao Xiang,1– 3 Lili Zhou,4 Rui Yang,1,4 Fang Yuan,1– 3 Yilin Xu,4 Yuan Yang,1,4 Yong Qiao,1– 3 Xin Li1– 3 1Department of Pharmacy, The Third Hospital of Changsha, Changsha, Hunan Province, People’s Republic of China; 2Hunan Provincial Key Laboratory of Anti-Resistance Microbial Drugs, Changsha, Hunan Province, People’s Republic of China; 3The Clinical Application Research Institute of Antibiotics in Changsha, Changsha, Hunan Province, People’s Republic of China; 4College of Pharmacy, Hunan University of Chinese Medicine, Changsha, Hunan Province, People’s Republic of ChinaCorrespondence: Xin Li, 176 Laodong West Road, Tianxin District, Changsha, Hunan Province, People’s Republic of China, Tel +86 0731-85171320, Email xin-li@cssdsyy.comAbstract: Currently, cancer remains one of the most significant threats to human health. Treatment of most cancers remains challenging, despite the implementation of diverse therapies in clinical practice. In recent years, research on the mechanism of ferroptosis has presented novel perspectives for cancer treatment. Ferroptosis is a regulated cell death process caused by lipid peroxidation of membrane unsaturated fatty acids catalyzed by iron ions. The rapid development of bio-nanotechnology has generated considerable interest in exploiting iron-induced cell death as a new therapeutic target against cancer. This article provides a comprehensive overview of recent advancements at the intersection of iron-induced cell death and bionanotechnology. In this respect, the mechanism of iron-induced cell death and its relation to cancer are summarized. Furthermore, the feasibility of a nano-drug delivery system based on iron-induced cell death for cancer treatment is introduced and analyzed. Secondly, strategies for inducing iron-induced cell death using nanodrug delivery technology are discussed, including promoting Fenton reactions, inhibiting glutathione peroxidase 4, reducing low glutathione levels, and inhibiting syst