Substrate Specificity of Adenine‐Cu‐PO₄ Nanozyme: Ascorbic Acid Oxidation and Selective Cytotoxicity.

Though nanozymes are becoming promising alternatives to natural enzymes due to their superior properties, constructing nanozyme with high specificity is still a great challenge. Herein, with Cu2+ as an active site and adenine as a ligand, Adenine‐Cu‐PO4 is synthesized in phosphate‐buffered saline. As an oxidase mimic, Adenine‐Cu‐PO4 could selectively catalyze oxidation of ascorbic acid (AA) to dehydroascorbic acid, but not universal substrates (3,3',5,5'‐tetramethylbenzidine (TMB), 2,2'‐azino‐bis (3‐ethylbenzthiazoline‐6‐sulfonic acid) (ABTS) and 2,4‐dichlorophenol (2,4‐DP)), small biomolecules (dopamine, glutathione, glucose, galactose), other vitamins (vitamin A acid, vitamin B1, vitamin K1) and even dithiothreitol (a common interference of AA). Such the specific AA catalytic oxidation is revealed that Adenine‐Cu‐PO4 selectively binds with AA through hydrogen bonds, accompanied with catalyzing AA oxidation, and concurrently O2 transferring to H2O2 via O2⋅−, further to H2O via ⋅OH. Based on the produced reactive oxygen species, with AA as a pro‐oxidant, Adenine‐Cu‐PO4 nanozyme efficiently triggers severe intratumor oxidative stress to induce tumor cell death. This work opens a new avenue to design intrinsic nanozymes with high specificity, and also presents a promising application in the field of AA oxidation induced cancer therapy. [ABSTRACT FROM AUTHOR]