Competitive Inhibition of the Enzyme-Mimic Activity of Gd-Based Nanorods toward Highly Specific Colorimetric Sensing of l-Cysteine

Abstract

Gd-based nanomaterials offer interesting magnetic properties and have been heavily investigated for magnetic resonance imaging. The applicability of these materials beyond biomedical imaging remains limited. The current study explores the applicability of these rare-earth nanomaterials as nanozyme-mediated catalysts for colorimetric sensing of l-cysteine, an amino acid of high biomedical relevance. We show a facile solution-based strategy to synthesize two Gd-based nanomaterials viz. Gd(OH) and GdO nanorods. We further establish the catalytic peroxidase-mimic nanozyme activity of these Gd(OH) and GdO nanorods. This catalytic activity was suppressed specifically in the presence of l-cysteine that allowed us to develop a colorimetric sensor to detect this biologically relevant molecule among various other contaminants. This suppression, which could either be caused due to catalyst poisoning or enzyme inhibition, prompted extensive investigation of the kinetics of this catalytic inhibition in the presence of cysteine. This revealed a competitive inhibition process, a mechanism akin to those observed in natural enzymes, bringing nanozymes a step closer to the biological systems.

L-Cysteine as an Irreversible Inhibitor of the Peroxidase-Mimic Catalytic Activity of 2-Dimensional Ni-Based Nanozymes

“…Of the different applications and fundamental investigations, one aspect that is gaining rapid attention is the ability to modulate the catalytic activity of nanozymes i.e., either enhance, deteriorate, temporarily inhibit or permanently inhibit its catalytic activity. To this end, metal ions [ 14 , 15 , 16 , 17 ], biomolecules such as ATP [ 18 , 19 , 20 ], cysteine [ 21 , 22 , 23 , 24 , 25 ], and glutathione [ 26 , 27 ] have all been successfully employed to modulate the catalytic activity of nanozymes. For instance, ATP was seen to enhance the catalytic activity of nanozymes while the amino acid cysteine was reported to inhibit their catalytic activity [ 18 , 21 ].…”

“…To this end, metal ions [ 14 , 15 , 16 , 17 ], biomolecules such as ATP [ 18 , 19 , 20 ], cysteine [ 21 , 22 , 23 , 24 , 25 ], and glutathione [ 26 , 27 ] have all been successfully employed to modulate the catalytic activity of nanozymes. For instance, ATP was seen to enhance the catalytic activity of nanozymes while the amino acid cysteine was reported to inhibit their catalytic activity [ 18 , 21 ]. In this context, inhibition of the nanozyme activity can be considered akin to natural enzymes where an inhibitor molecule binds either to the active site of the enzyme or away from the active site of the enzyme resulting in complete loss of the catalytic activity or lowering the catalytic efficiency [ 28 ].…”

“…Our group and others have previously established that L-cysteine can act as a nanozyme inhibitor, thereby inactivating the peroxidase-mimic catalytic activity resulting in a turn-off nanozyme sensor [ 21 , 22 , 24 , 32 ]. Most of these studies suggested that L-cysteine shields the surface of the nanozyme from the colorimetric substrate resulting in the loss of catalytic activity [ 22 , 32 ].…”

“…Most of these studies suggested that L-cysteine shields the surface of the nanozyme from the colorimetric substrate resulting in the loss of catalytic activity [ 22 , 32 ]. Our group was the first to show that in the case of Gd(OH) 3 nanozyme, L-cysteine acts as a competitive inhibitor molecule for the nanozyme substrate which results in temporary inactivation of the catalytic activity [ 21 ]. While the investigation of the underlying mechanism has provided some understanding of the complex molecular interactions, it is still unclear if most nanozymes will reversibly interact with L-cysteine and if L-cysteine interacts reversibly, what is the mechanism of this reversible inhibition?…”

Cu@Au(Ag)/Pt nanocomposite as peroxidase mimic and application of Cu@Au/Pt in colorimetric detection of glucose and l-cysteine

“…Literature reported L-cysteine could inhibit the peroxidaselike activity of nanoparticles through interaction of metal atoms in the surface of nanoparticles with -SH of cysteine. 47,48 Therefore, we investigated the possibility for the detection of Lcysteine using Cu@Au/Pt nanocomposite. Interestingly, when cysteine was added to the mixture of Cu@Au/Pt + TMB + H 2 O 2 , the color changed from blue to colorless and the absorbance at 652 nm decreased signicantly, indicating that addition of cysteine inhibited the oxidation of TMB.…”