Simultaneous Fenton‐like Ion Delivery and Glutathione Depletion by MnO₂‐Based Nanoagent to Enhance Chemodynamic Therapy

Abstract

Chemodynamic therapy (CDT) utilizes iron-initiated Fenton chemistry to destroy tumor cells by converting endogenous H O into the highly toxic hydroxyl radical ( OH). There is a paucity of Fenton-like metal-based CDT agents. Intracellular glutathione (GSH) with OH scavenging ability greatly reduces CDT efficacy. A self-reinforcing CDT nanoagent based on MnO is reported that has both Fenton-like Mn delivery and GSH depletion properties. In the presence of HCO , which is abundant in the physiological medium, Mn exerts Fenton-like activity to generate OH from H O . Upon uptake of MnO -coated mesoporous silica nanoparticles (MS@MnO NPs) by cancer cells, the MnO shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn , resulting in GSH depletion-enhanced CDT. This, together with the GSH-activated MRI contrast effect and dissociation of MnO , allows MS@MnO NPs to achieve MRI-monitored chemo-chemodynamic combination therapy.

A GSH‐Gated DNA Nanodevice for Tumor‐Specific Signal Amplification of microRNA and MR Imaging–Guided Theranostics

“…Under the dual guide of miRNA‐21 detection and MR imaging, GSH‐enhanced Fenton‐like reaction for chemodynamic therapy (CDT) was subsequently analyzed. The nanodevice with the assistance of HCO 3 − (abundant in physiological medium) showed GSH‐activated reactive oxygen species (ROS) production capability under a high concentration of H 2 O 2 , which was verified by the methylene blue (MB) degradation in the Figure A. However, little degradation of MB was observed without GSH.…”

Recent Progress in Ferroptosis Inducers for Cancer Therapy

“…ROS is a group of molecules containing partially reduced oxygen, including peroxides (H 2 O 2 , ROOH), superoxide (O 2 − ·), singlet oxygen ( 1 O 2 ), and free radicals (HO·, HO 2 ·, R·, RO·, NO·, and NO 2 ·), which are able to cause cancer cell death by damaging biomolecules like DNA/RNA, proteins and lipids . ROS involved in ferroptosis can be generated from various sources, and the accumulation of oxidative products (especially phospholipid hydroperoxides) is considered as a hallmark of ferroptosis .…”

“…Before ferroptosis was defined in 2012, nanotechnology had been explored to treat cancers by modulating the metabolism in TME. In particular, chemodynamic therapy (CDT) based on the initiation of Fenton chemistry to upregulate ROS levels can induce oxidative stress in cancer cells and drive cell death . FDA‐approved iron‐supplementing agent ferumoxytol (Feraheme) has been proved effective in inhibiting early cancers and cancer metastasis by depolarizing macrophage into pro‐inflammatory M1 phenotypes .…”

One‐Dimensional Fe2P Acts as a Fenton Agent in Response to NIR II Light and Ultrasound for Deep Tumor Synergetic Theranostics

“…[1] COH radicals are generally considered to be the most toxic ROS, which can be produced by the Fenton reaction in the presence of H 2 O 2 and Fenton agents. [1] COH radicals are generally considered to be the most toxic ROS, which can be produced by the Fenton reaction in the presence of H 2 O 2 and Fenton agents.…”