Nano-formulations in therapeutic strategies targeting cancer ferroptosis

Ferroptosis is a cell death mode caused by excessive accumulation of lipid peroxides (LPOs) due to intracellular metabolic pathway disorder, which is closely related to intracellular iron metabolism and lipid homeostasis. In cancer therapy, this metabolic imbalance promotes the clearance of tumor cells, suggesting that ferroptosis exerts a tumor suppressor function. However, the clinical translation of ferroptosis-based strategies in oncology is currently hindered by challenges such as inadequate therapeutic efficacy. In the past five years, the rational design of nano-formulations to induce cancer ferroptosis combined with other emerging therapeutic modalities (chemotherapy (CT), chemodynamic therapy (CDT), photodynamic therapy (PDT), sonodynamic therapy (SDT), and immunotherapy) has achieved promising therapeutic effects in many rodent tumor models. This review summarizes the recent progress of novel nano-formulations for cancer ferroptosis therapy. The multiple mechanisms and detection indicators of cancer cells during ferroptosis, the rational design of novel nano-formulations, and their strategies for inducing cancer ferroptosis will be introduced. Finally, the challenges and prospects of utilizing novel nano-formulations for cancer ferroptosis therapy will be discussed.