Synergistic Functional Nanomedicine Enhances Ferroptosis Therapy for Breast Tumors by a Blocking Defensive Redox System.
Sijin ChenJing YangZhiyu LiangZongheng LiWei XiongQingdeng FanZheyu ShenJianping LiuYikai XuPublished in: ACS applied materials & interfaces (2023)
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 Fe 2+ -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.
Keyphrases
- cell death
- cancer therapy
- aqueous solution
- quantum dots
- papillary thyroid
- cell cycle arrest
- reactive oxygen species
- squamous cell
- drug delivery
- water soluble
- iron oxide nanoparticles
- electron transfer
- cell proliferation
- photodynamic therapy
- poor prognosis
- squamous cell carcinoma
- wastewater treatment
- drug induced
- stem cells
- diabetic rats
- mesenchymal stem cells
- gold nanoparticles
- oxidative stress
- young adults
- long non coding rna
- nitric oxide