A Hollow Nucleobase Coordinated Nanozyme for Tumor Catalytic Therapy.

Coordination nanozymes have emerged as promising candidates for catalytic therapy due to their versatility and distinctive catalytic performance. To amplify catalytic efficiency, structural engineering of nanozymes through hollow architectures has emerged as a pivotal strategy by maximizing active site accessibility and optimizing substrate diffusion kinetics. However, conventional synthetic routes necessitate extreme chemical conditions and complex processes, hindering the functional integration of biomolecule. Herein, a template-free self-assembly strategy is developed to construct hollow Au-adenine coordination polymers (HAuA CPs) through ethanol-induced reconstruction at ambient temperature. By optimizing HAuCl4-adenine coordination chemistry, precursors formed within 8 minutes in aqueous solution, followed by ligand displacement-driven structural evolution to yield hollow architectures with specific shell thickness. Density functional theory calculations reveal ethanol molecules competitively weaken Au-N/Cl bonds, enabling spontaneous hollowing. The optimized HAuA CPs exhibits 1.75-fold enhanced oxidase-like activity and catalase-like functionality modulated by pH, compared to solid counterparts. Crucially, this mild synthesis preserved activity of encapsulated glucose oxidase, achieving 31.7-fold reactive oxygen species generation. In vivo experiment prove that the system induce significant tumor growth inhibition (83.3%). This work establishes a green and universal synthesis strategy for hollow coordination nanozymes and provides mechanistic insights into structure control of coordination nanozymes for advanced catalytic therapeutics.