Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System.

Abstract

The upregulation of dihydroorotate dehydrogenase (DHODH) redox systems inside tumor cells provides a powerful shelter against lipid peroxidation (LPO), impeding ferroptosis-induced antitumor responses. To solve this issue, we report a strategy to block redox systems and enhance ferroptotic cancer cell death based on a layered double hydroxide (LDH) nanoplatform (siR/IONs@LDH) co-loaded with ferroptosis agent iron oxide nanoparticles (IONs) and the DHODH inhibitor (siR). siR/IONs@LDH is able to simultaneously release IONs and siR in a pH-responsive manner, efficiently generate toxic reactive oxygen species (ROS) via an Fe2+-mediated Fenton reaction, and synergistically induce cancer cell death upon the acceleration of LPO accumulation. In vivo therapeutic evaluations demonstrate that this nanomedicine has excellent performance for tumor growth inhibition without any detectable side effects. This work thus provides a new insight into nanomaterial-mediated tumor ferroptosis therapy.

• Authors: Sijin Chen, Jing Yang, Zhiyu Liang, Zongheng Li, Wei Xiong, Qingdeng Fan, Zheyu Shen, Jianping Liu, Yikai Xu
• Journal: ACS applied materials & interfaces (ACS Appl Mater Interfaces) Vol. 15 Issue 2 Pg. 2705-2713 (Jan 18 2023) ISSN: 1944-8252 [Electronic] United States
• PMID: 36622364 (Publication Type: Journal Article)

Chemical References

• Dihydroorotate Dehydrogenase
• Reactive Oxygen Species

Topics

• Female
• Humans
• Breast Neoplasms (drug therapy)
• Cell Line, Tumor
• Dihydroorotate Dehydrogenase (antagonists & inhibitors)
• Ferroptosis
• Nanomedicine (methods)
• Nanoparticles (therapeutic use)
• Oxidation-Reduction
• Reactive Oxygen Species (metabolism)
• Magnetic Iron Oxide Nanoparticles