Ferroptosis is an alternative strategy to overcome chemoresistance, but effective therapeutic approaches to induce ferroptosis for acute myeloid leukemia (AML) treatment are limited. Here, we developed glutathione (GSH)-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an efficient ferroptosis inducer and chemotherapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4, a GSH-dependent hydroperoxidase, to cause lipid peroxidation and ferroptosis in AML cells. Furthermore, GCFN-loaded paclitaxel (PTX@GCFN) targeted AML cells and spared normal hematopoietic cells to limit the myeloablation side effects caused by paclitaxel. PTX@GCFN treatment extended the survival of AML mice by specifically releasing paclitaxel and simultaneously inducing ferroptosis in AML cells with restricted myeloablation and tissue damage side effects. Overall, the dual-functional GCFN acts as an effective ferroptosis inducer and a chemotherapeutic drug carrier for AML treatment.
Keyphrases
- acute myeloid leukemia
- cell death
- cell cycle arrest
- induced apoptosis
- allogeneic hematopoietic stem cell transplantation
- drug delivery
- oxidative stress
- fluorescent probe
- emergency department
- signaling pathway
- adipose tissue
- mesenchymal stem cells
- acute lymphoblastic leukemia
- nitric oxide
- spinal cord
- skeletal muscle
- cell proliferation
- insulin resistance
- cell therapy
- replacement therapy