Stimuli‐Responsive Manganese Single‐Atom Nanozyme for Tumor Therapy via Integrated Cascade Reactions

Abstract

The single‐atom enzyme (SAE) is a novel type of nanozyme that exhibits extraordinary catalytic activity. Here, we constructed a PEGylated manganese‐based SAE (Mn/PSAE) by coordination of single‐atom manganese to nitrogen atoms in hollow zeolitic imidazolate frameworks. Mn/PSAE catalyzes the conversion of cellular H2O2 to .OH through a Fenton‐like reaction; it also promotes the decomposition of H2O2 to O2 and continuously catalyzes the conversion of O2 to cytotoxic .O2− via oxidase‐like activity. The catalytic activity of Mn/PSAE is more pronounced in the weak acidic tumor environment; therefore, these cascade reactions enable the sufficient generation of reactive oxygen species (ROS) and effectively kill tumor cells. The prominent photothermal conversion property of the amorphous carbon can be utilized for photothermal therapy. Hence, Mn/PSAE exhibits significant therapeutic efficacy through tumor microenvironment stimulated generation of multiple ROS and photothermal activity.

Pd‐Single‐Atom Coordinated Biocatalysts for Chem‐/Sono‐/Photo‐Trimodal Tumor Therapies

“…Recently, single-atom catalysts possessing atomically dispersed metal active sites have made a breakthrough in the broad fields of catalysis owing to their maximum metal atom utilization, high selectivity, and activity. [34][35][36][37][38] As mentioned above, activating localized H 2 O 2 in the TME by biocatalytic nanoagents can achieve very high CDT antitumor efficiency; recently, the Zn, Fe, and Cu single-atoms-doped nanocarbon catalysts have been designed and studied for wound healing and antitumor therapies. [39,40] While these carbon-based nanoagents are nonbiodegradable and show a low doping amount of single atoms.…”

Recent Advances of Manganese-Based Hybrid Nanomaterials for Cancer Precision Medicine

“…Many Mn-based hybrid nanomaterials used for imagingguided PTT have been developed (11,48,71,(73)(74)(75)(76)(77), such as nanopetals of Mn 3 O 4 hybrid nanomaterials for multifunctional imaging-guided PTT (51), a 2-D nanoplatform based on Cu 2 MnS 2 nanoplates for MRI/multispectral optoacoustic tomography (MSOT) dual-modal imaging-guided PTT (52,78), a plasmonic modulation strategy of Gold Nanorods (GNRs) through MnO 2 coating for TME-responsive photoacoustic (PA)/MR duplex imaging guided NIR-II PTT (67), and a gold@ MnO 2 (Au@ MnO 2 ) core-shell nanostructure as a GSH-triggered smart theranostic agent for PA and MR dual imaging-guided PTT (53,68).…”

Single‐Atom Pd Nanozyme for Ferroptosis‐Boosted Mild‐Temperature Photothermal Therapy

“…[20] Inspired by the highly active single-atom catalysts,s uch as Mn-based singleatom enzyme, [21] we thought that the single atom nanozyme (SAzyme) with enhanced dual POD and GSHOx-mimicking enzyme activities would greatly increase the intracellular ROSl evel. [22] Furthermore,t he GSH depletion inactivates glutathione peroxidase 4( GPX4) protease,w hich finally causes the up-regulation of lethal LPO accompanied by the generation of plentiful ROSf or executing ferroptosis. [23] Notably,t he accumulation of LPO and ROSp rovides apowerful approach for cleaving HSPs.Herein, we prepared nitrogen-coordinated carbon-supported Pd SAzyme by striping single atom from metal nanoparticles (Scheme 1).…”

“…successively demonstrated the distinguished properties of single‐atom catalysts, which heralds a new era of atomic nanotechnologies [20] . Inspired by the highly active single‐atom catalysts, such as Mn‐based single‐atom enzyme, [21] we thought that the single atom nanozyme (SAzyme) with enhanced dual POD and GSHOx‐mimicking enzyme activities would greatly increase the intracellular ROS level [22] . Furthermore, the GSH depletion inactivates glutathione peroxidase 4 (GPX4) protease, which finally causes the up‐regulation of lethal LPO accompanied by the generation of plentiful ROS for executing ferroptosis [23] .…”