Iron-doxorubicin prodrug loaded liposome nanogenerator programs multimodal ferroptosis for efficient cancer therapy.

ABSTRACT: Ferroptosis is a new mode of cell death, which can be induced by Fenton reaction-mediated lipid peroxidation. However, the insufficient H₂O₂ and high GSH in tumor cells restrict the efficiency of Fenton reaction-dependent ferroptosis. Herein, a self-supplying lipid peroxide nanoreactor was developed to co-delivery of doxorubicin (DOX), iron and unsaturated lipid for efficient ferroptosis. By leveraging the coordination effect between DOX and Fe³⁺, trisulfide bond-bridged DOX dimeric prodrug was actively loaded into the core of the unsaturated lipids-rich liposome via iron ion gradient method. First, Fe³⁺could react with the overexpressed GSH in tumor cells, inducing the GSH depletion and Fe²⁺generation. Second, the cleavage of trisulfi

SUBMITTER: Yang Y 

PROVIDER: S-EPMC8737402 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature