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 H2O2 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 MnO2 is reported that has both Fenton‐like Mn2+ delivery and GSH depletion properties. In the presence of HCO3−, which is abundant in the physiological medium, Mn2+ exerts Fenton‐like activity to generate .OH from H2O2. Upon uptake of MnO2‐coated mesoporous silica nanoparticles (MS@MnO2 NPs) by cancer cells, the MnO2 shell undergoes a redox reaction with GSH to form glutathione disulfide and Mn2+, resulting in GSH depletion‐enhanced CDT. This, together with the GSH‐activated MRI contrast effect and dissociation of MnO2, allows MS@MnO2 NPs to achieve MRI‐monitored chemo–chemodynamic combination therapy.

Bacterial Template Synthesis of Multifunctional Nanospindles for Glutathione Detection and Enhanced Cancer-Specific Chemo-Chemodynamic Therapy

“…It was worth noting that Hcy and Cys, the two biological thiols that may severely affect GSH detection, did not interfere with the GSH detection in our system. /HCO 3 − ) buffer solution are all necessary to fade the blue MB solution, which was in accordance with the previous work [58]. Additionally, the results of groups 4 and 5 indicated that the added GSH eliminated the formed ⋅ OH and inhibited the MB degradation.…”

“…However, at high DOX concentrations (10-20 μg mL −1 ), EMD NSs showed the relatively higher cytotoxicity than free DOX ( Figure 5(h)), so we assumed that some other factors may also play roles in the EMD NS-induced cell death. Although EM NSs caused negligible changes in the cell viabilities, the substantial accumulation of ROS was observed in the EM NS-or EMD NS-treated cells (Figure 5(l) and Figure S13), which could be attributed to the conversion of endogenous H 2 O 2 to highly reactive ⋅ OH (one of the most harmful forms of ROS) induced by the Mn 2+ -mediated Fenton-like reaction [58]. Importantly, based on the in vitro EM NS-assisted O 2 generation results (Figure 4(a)), EM NSs showed great promise in downregulating the P-gp expression by increasing the O 2 level under hypoxia.…”

“…Additionally, chemodynamic therapy (CDT), as an emerging therapeutic strategy using the in situ Fenton reaction or Fenton-like reaction to generate hydroxyl radical ( ⋅ OH) to induce cell apoptosis, has attracted much attention due to its high selectivity and lethality activated by internal stimuli [53][54][55][56][57]. Apart from the commonly used iron ions that can induce Fenton reaction, other metal ions including Mn 2+ , Co 2+ , and Cu 2+ also show Fenton-like activity [58,59], which can be developed to be new types of chemodynamic nanoagents.…”

Photoacoustic Therapy for Precise Eradication of Glioblastoma with a Tumor Site Blood–Brain Barrier Permeability Upregulating Nanoparticle

“…Several alternative therapies have been proposed and investigated in the treatment of glioblastoma. Phototherapy, utilizing a light‐powered photochemical reaction as in photodynamic therapy (PDT), and localized hyperthermia have attracted considerable attention as alternatives to conventional radiotherapy and chemotherapy . The photoacoustic (PA) shockwave, created by the cavitation (growth and collapse) of nanobubbles and microbubbles around nanoparticles heated by laser pulses, produces a strong and localized mechanical disruption of the tissue it comes into contact with .…”

Dual pH-sensitive nanodrug blocks PD-1 immune checkpoint and uses T cells to deliver NF-κB inhibitor for antitumor immunotherapy

“…It is well known that MnO 2 is stable in the bloodstream with low r 1 and r 2 values. However, it can react with TME-enriched acid and H 2 O 2 to generate Mn 2+ , which is a potent MRI T 1 contrast agent (20). The above results indicated that the aPD-1-decorated nanomicelle (MnO 2 @PPC-aPD-1) accumulated much more effectively in the tumor sites of animals with CUR pretreatment (the CT-aPD-1 group) than the antibody isotype-decorated nanomicelle (MnO 2 @ PPC-Iso) in the tumor sites of animals with CUR pretreatment (the CT-Iso group) or without CUR pretreatment (the NCT-Iso group).…”