Eriodictyol-cisplatin coated nanomedicine synergistically promote osteosarcoma cells ferroptosis and chemosensitivity

Eriodictyol-cisplatin coated nanomedicine synergistically promote osteosarcoma cells ferroptosis and chemosensitivity

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Abstract The ever-increasing chemoresistance of osteosarcoma (OS) has been observed in the recent decades, impeding OS therapeutic improvement and posing an chicago cubs earrings urgency to exploit to the alternative and/or supplementary therapies for the optimization of OS chemotherapeutic regimen.Ferroptosis, a regulated cell death, has been identified as a natural anticancer mechanism as well as a synergist for chemotherapeutics in various cancers.Herein, we affirmed the tumor-suppressing properties of eriodictyol and illustrated that its antitumor effects might ascribe to the ferroptosis-inducing activity, in which eriodictyol could bind with BACH1 to repress the transcription and translation of GPX4 and eventually result in the GPX4-related ferroptosis.Further investigation found that eriodictyol could exhibit a synergistic effect with cisplatin, facilitating the antitumor effects of cisplatin.Lastly, through utilizing hollow mesoporous prussian blue nanocubes loaded with eriodictyol and cisplatin, we formed the ferroptosis-synergistic nanocomplexes to facilitate OS cells ferroptosis and cisplatin sensitivity.

Through direct catalytic oxidation of unsaturated lipids, exogenous iron delivery, GSH exhaustion, cartoon martian with big head and GPX4 transcriptional inhibition, this ferroptosis-synergistic nanocomplex could excellently enhance OS cells ferroptosis in both vitro and vivo, with no obvious organ injury observed.Therefore, our ferroptosis-synergistic nanocomplex may represent a promising alternative therapeutic strategy for OS patients.Graphical Abstract.