Affiliation:
1. National Key Laboratory of Veterinary Public Health and Safety College of Veterinary Medicine China Agricultural University Beijing 100193 P.R. China
2. Department of Animal Pharmacy College of Veterinary Medicine Shandong Agricultural University Tai'an Shandong 271018 P. R. China
3. Department of Pharmacology Biodiscovery Institute Monash University Victoria 3800 Australia
Abstract
AbstractMetal‐organic framework (MOF)‐based drug delivery nanomaterials for cancer therapy have attracted increasing attention in recent years. Here, an enhanced chemodynamic anti‐tumor therapy strategy by promoting the Fenton reaction by using core‐shell zeolitic imidazolate framework‐8 (ZIF‐8)@Fe3O4 as a therapeutic platform is proposed. Carboxymethyl cellulose (CMC) is used as a stabilizer of Fe3O4, which is then decorated on the surface of ZIF‐8 via the electrostatic interaction and serves as an efficient Fenton reaction trigger. Meanwhile, the pH‐responsive ZIF‐8 scaffold acts as a container to encapsulate the chemotherapeutic drug doxorubicin (DOX). The obtained DOX‐ZIF‐8@Fe3O4/CMC (DZFC) nanoparticles concomitantly accelerate DOX release and generate more hydroxyl radicals by targeting the lysosomes in cancer cells. In vitro and in vivo studies verify that the DZFC nanoparticles trigger glutathione peroxidase 4 (GPX4)‐dependent ferroptosis via the activation of the c‐Jun N‐terminal kinases (JNK) signaling pathway, following to achieve the chemo/ferroptosis synergistic anti‐tumor efficacy. No marked toxic effects are detected during DZFC treatment in a tumor‐bearing mouse model. This composite nanoparticle remarkably suppresses the tumor growth with minimized systemic toxicity, opening new horizons for the next generation of theragnostic nanomedicines.
Funder
National Natural Science Foundation of China
Cited by
4 articles.
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