Catalytically potent and selective clusterzymes for modulation of neuroinflammation through single-atom substitutions

Abstract

Emerging artificial enzymes with reprogrammed and augmented catalytic activity and substrate selectivity have long been pursued with sustained efforts. The majority of current candidates have rather poor catalytic activity compared with natural molecules. To tackle this limitation, we design artificial enzymes based on a structurally well-defined Au25 cluster, namely clusterzymes, which are endowed with intrinsic high catalytic activity and selectivity driven by single-atom substitutions with modulated bond lengths. Au24Cu1 and Au24Cd1 clusterzymes exhibit 137 and 160 times higher antioxidant capacities than natural trolox, respectively. Meanwhile, the clusterzymes demonstrate preferential enzyme-mimicking catalytic activities, with Au25, Au24Cu1 and Au24Cd1 displaying compelling selectivity in glutathione peroxidase-like (GPx-like), catalase-like (CAT-like) and superoxide dismutase-like (SOD-like) activities, respectively. Au24Cu1 decreases peroxide in injured brain via catalytic reactions, while Au24Cd1 preferentially uses superoxide and nitrogenous signal molecules as substrates, and significantly decreases inflammation factors, indicative of an important role in mitigating neuroinflammation.

Catalytically Active Gold Clusters with Atomic Precision for Noninvasive Early Intervention of Neurotrauma

“…In addition, the zeta potentials of all nanoclusters were around − 35 mV (Fig. 1f), consistent with our previous work [29,49]. These results indicate the ultrasmall size and good colloid stability of nanoclusters, showing the potential in biological applications.…”

“…With the combination of our previous work [29], we concluded that the Au 24 Cd 1 and Au 24 Cu 1 nanoclusters exhibited selectivity on ROS and RNS and showed selective SOD-like and CAT-like activities, which can reduce the oxidative stress induced by brain injury and perform the therapeutic effect (Fig. 4a).…”

“…Especially, the ceria nanozymes exhibited enzymatic activities like SOD and CAT on scavenging RONS via redox cycle between Ce 4+ and Ce 3+ [12,18,25,28]. Gold nanoclusters can simulate SOD, CAT and GPx enzymes displaying compelling effects in TBI treatment with superb antioxidant capacities [29][30][31][32][33]. Besides, diagnosis and monitoring methods based on nanotechnologies especially activable nanoprobes are being developed for TBI [34][35][36], and technologies like atom engineering, surface modi cation, and size modulation were employed to promote the activity and utilization of nanozymatic biocatalysts [30][31][32][37][38][39][40][41][42][43][44].…”

“…4a). Additionally, the Au 24 Cd 1 and Au 24 Cu 1 nanoclusters presented favorable biocompatibility and metabolic properties, which bene ts their use in vivo [29]. The behavior tests were conducted to evaluate the spatial learning and memory abilities by Morris water maze (Fig.…”

“…In conclusion, our work showed the great potential of noninvasive early intervention for the treatment of TBI with enzymatic biocatalysts. Au 24 Cu 1 and Au 24 Cd 1 nanoclusters were prepared as per the previous report[29, 61, 62]. Brie y, HAuCl 4 (aqueous, 20 mM, 0.25 mL) and MPA (aqueous, 5 mM, 2 mL) were added to water (2.35 mL) and stirred for 5 min at room temperature.…”