Biocompatible Ruthenium Single-Atom Catalyst for Cascade Enzyme-Mimicking Therapy

Abstract

Rationally constructing single-atom enzymes (SAEs) with superior activity, robust stability, and good biocompatibility is crucial for tumor therapy but still remains a substantial challenge. In this work, we adopt biocompatible carbon dots as the carrier material to load Ru single atoms, achieving Ru SAEs with superior multiple enzyme-like activity and stability. Ru SAEs behave as oxidase, peroxidase, and glutathione oxidase mimics to synchronously catalyze the generation of reactive oxygen species (ROS) and the depletion of glutathione, thus amplifying the ROS damage and finally causing the death of cancer cells. Notably, Ru SAEs exhibit excellent peroxidaselike activity with a specific activity of 7.5 U/mg, which surpasses most of the reported SAEs and is 20 times higher than that of Ru/C. Theoretical results reveal that the electrons of the Ru 4d orbital in Ru SAEs are transferred to O atoms in H 2 O 2 and then efficiently activate H 2 O 2 to produce • OH. Our work may provide some inspiration for the design of SAEs for cancer therapy.

Shape Regulation of CeO2 Nanozymes Boosts Reaction Specificity and Activity

“…A strong signal at this wavelength can be observed for the octahedron CeO 2 followed by the sphere and cube, suggesting their ALP‐like activity in the order of octahedron>sphere>cube. A similar trend (i. e., octahedron>cube) was also reported previously using NPP as the substrate [18,20] . For the POD‐like reaction associated with the redox between OPD and H 2 O 2 (Figure 1e), the formation of diaminophenazine (DAP) with an emission peak centered at 557 nm was monitored.…”

“…A similar trend (i. e., octahedron > cube) was also reported previously using NPP as the substrate. [18,20] For the POD-like reaction associated with the redox between OPD and H 2 O 2 (Figure 1e), the formation of diaminophenazine (DAP) with an emission peak centered at 557 nm was monitored. Interestingly, CeO 2 shapes displayed an opposite trend in their POD-like activity (i. e., cube > sphere > octahedron) similar to that of using TMB as the substrate (i. e., cube > octahedron).…”

“…Previous studies on the activity of CeO 2 nanozymes often relied on colorimetric substrates such as nitrophenyl phosphate (NPP) for the ALP-like reaction [18][19][20] and tetramethylbenzidine (TMB) for the POD-like reaction. [11][12][13][14][15] Considering that fluorescent probes have become indispensable for bio/molecular imaging with much higher sensitivity compared to that of colorimetric probes, we, therefore, evaluated the ALP-like and POD-like activity of CeO 2 using fluorogenic substrates, 4-methylumbelliferyl phosphate (4-MUP, at pH = 7.2) and o-phenylenediamine (OPD, at pH = 4.5).…”

“…[4] Up to date, many transition metal oxides with switchable oxidation states (e. g., V 2 O 5 , [5] Mn 3 O 4 , [6] Fe 2 O 3 , [7] Co 3 O 4 , [8] NiO, [9] Cu 2 O, [10] and CeO 2 [11][12][13][14][15] ) have been reported to exhibit this peroxidase (POD)-like activity even in their single atom form. [16][17][18][19][20][21][22] Interestingly, CeO 2 is the only reducible transition metal oxide that can mimic alkaline phosphatase (ALP) in catalyzing the hydrolysis of phosphorylated molecules [23][24][25][26][27] as that of non-reducible ZrO 2 . [28] Given that these two enzyme-like reactions undergo different catalytic mechanisms, it would be very interesting if one could precisely manipulate the reaction specificity on a pristine CeO 2 .…”

“…Among them, nanomaterials with enzyme‐like characteristics (also called nanozymes) have received increasing attention [2,3] since Fe 3 O 4 nanoparticles (NPs) was found to oxidize a given substrate with H 2 O 2 as that of horseradish peroxidase (2007) [4] . Up to date, many transition metal oxides with switchable oxidation states (e. g., V 2 O 5 , [5] Mn 3 O 4 , [6] Fe 2 O 3 , [7] Co 3 O 4 , [8] NiO, [9] Cu 2 O, [10] and CeO 2 [11–15] ) have been reported to exhibit this peroxidase (POD)‐like activity even in their single atom form [16–22] . Interestingly, CeO 2 is the only reducible transition metal oxide that can mimic alkaline phosphatase (ALP) in catalyzing the hydrolysis of phosphorylated molecules [23–27] as that of non‐reducible ZrO 2 [28] …”