Coordination-Driven Self-Assembly Strategy-Activated Cu Single-Atom Nanozymes for Catalytic Tumor-Specific Therapy

How to optimize the enzyme-like catalytic activity of nanozymes to improve their applicability has become a great challenge. Herein, we present an L-cysteine (L-Cys) coordination driven self-assembly strategy to activate polyvinylpyrrolidone (PVP)-modified Cu single-atom nanozymes MoOx-Cu-Cys (denoted as MCCP SAzymes) aiming at catalytic tumor-specific therapy. The Cu single atom content of MCCP can be rationally modulated to 10.10 wt %, which activates the catalase (CAT)-like activity of MoOx nanoparticles to catalyze the decomposition of H2O2 in acidic microenvironments to increase O2 production. Excitingly, the maximized CAT-like catalytic efficiency of MCCP is 138-fold higher than that of typical MnO2 nanozymes and exhibits 14.3-fold higher affinity than natural catalase, as demonstrated by steady-state kinetics. We verify that the well-defined L-Cys-Cu center dot center dot center dot O active sites optimize CAT-like activity to match the active sites of natural catalase through an L-Cys bridge-accelerated electron transfer from Cys-Cu to MoOx disclosed by density functional theory calculations. Simultaneously, the high loading Cu single atoms in MCCP also enable generation of center dot OH via a Fenton-like reaction. Moreover, under X-ray irradiation, MCCP converts O2 to 1O2 for cascading radiodynamic therapy, thereby facilitating the multiple reactive oxygen species (ROS) for radiosensitization to achieve substantial antitumor.

Automated summary

A coordination driven self-assembly strategy using L-cysteine was presented to activate PVP-modified Cu single-atom nanozymes for catalytic tumor-specific therapy. The optimized catalase-like activity of the nanozymes was achieved by modulating the Cu single atom content and the L-Cys-Cu center dot center dot center dot O active sites. The nanozymes exhibited significantly higher catalytic efficiency compared to typical MnO2 nanozymes and natural catalase.