Atomic Engineering of Clusterzyme for Relieving Acute Neuroinflammation through Lattice Expansion

Abstract

Natural enzymes are efficient and versatile biocatalysts but suffer in their environmental tolerance and catalytic stability. As artificial enzymes, nanozymes can improve the catalytic stability, but it is still a challenge to achieve high catalytic activity. Here, we employed atomic engineering to build the artificial enzyme named Au24Ag1 clusterzyme that hosts an ultrahigh catalytic activity as well as strong physiological stability via atom manipulation. The designed Au24Ag1 clusterzyme activates the Ag–S active site via lattice expansion in the oligomer atom layer, showing an antioxidant property 72 times higher than that of natural antioxidant Trolox. Enzyme-mimicked studies find that Au24Ag1 clusterzyme exhibits high catalase-like (CAT-like) and glutathione peroxidase-like (GPx-like) activity with a maximum reaction rate of 68.9 and 17.8 μM/min, respectively. Meanwhile, the unique catalytic landscape exhibits distinctive reactions against inflammation by inhibiting the cytokines at an early stage in the brain. Atomic engineering of clusterzymes provides a powerful and attractive platform with satisfactory atomic dispersion for tailoring biocatalysts freely at the atomic level.

High Stability Au NPs: From Design to Application in Nanomedicine

“…240 Recent studies have shown that the atomic-level Au 24 Ag 1 cluster enzyme has ultra-high physiological stability and its unique CAT and GPxlike enzyme activities can effectively inhibit inflammatory molecules in the brain, which is expected to play an essential role in nanomedicine. 241 On the other side, antibacterial is an essential property of nanozymes. Ultra-small size (<2 nm) Au NPs have been found to interact with bacteria and destroy their cell membrane.…”

Catalytically active gold clusters with atomic precision for noninvasive early intervention of neurotrauma

“…Unlike traditional nanozyme, bioactive gold clusters exhibit the high efficient renal clearance and negligible toxicity even at very high injected dose (500 mg/kg) [24,25,27]. Moreover, due to ultrasmall size, the gold clusters can enter cell or injury site easily, resulting in high efficient treatment [26,28]. Gold clusters possess activities like SOD, CAT and GPx enzymes, performing significant antioxidant effects in TBI treatment [26,[28][29][30][31].…”

“…Moreover, due to ultrasmall size, the gold clusters can enter cell or injury site easily, resulting in high efficient treatment [26,28]. Gold clusters possess activities like SOD, CAT and GPx enzymes, performing significant antioxidant effects in TBI treatment [26,[28][29][30][31]. Though nanotechnologies for TBI diagnosis and monitoring were employed to promote the activity and utilization of nanozymatic biocatalysts like atom engineering, surface modification, and size modulation [32][33][34], it remains painless and chanllenged for clinical translation [12,15,[29][30][31][35][36][37][38][39][40][41][42][43][44][45].…”

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

“…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].…”

“…Compared with the TBI group, all nanoclusters promoted the healing progress among which the Au 24 Cd 1 presented the best healing effect followed by Au 24 Cu 1 , demonstrating the therapeutic effect of the nanoclusters especially the Au 24 Cd 1 and Au 24 Cu 1 . In addition, we evaluated the oxidative stress-related indicators, including SOD, GSH/GSSG, MDA, and H 2 O 2 in TBI mice after nanoclusters treatment[33,57].TBI can consume lots of SOD and GSH, leading to the decrease of SOD and GSH activity and the increase of MDA and H 2 O 2 amount (Fig.5c-f). The presence of over-excessive MDA H 2 O 2 and GSSG indicates severe oxidative stress in TBI mice.…”