期刊
ACS NANO
卷 17, 期 4, 页码 3334-3345出版社
AMER CHEMICAL SOC
DOI: 10.1021/acsnano.2c06313
关键词
ferroptosis; drug targeting; leukemia; chemotherapy; myeloablation
The study developed GSH-responsive cysteine polymer-based ferroptosis-inducing nanomedicine (GCFN) as an effective therapy for acute myeloid leukemia (AML). GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4 to induce ferroptosis in AML cells. PTX@GCFN targeted AML cells and reduced myeloablation side effects caused by paclitaxel, leading to extended survival of AML mice with simultaneous ferroptosis induction.
Ferroptosis is an alternative strategy to overcome chemo-resistance, 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 chemo-therapeutic drug nanocarrier for AML treatment. GCFN depleted intracellular GSH and inhibited glutathione peroxidase 4, a GSH-dependent hydro-peroxidase, 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.
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