Substrate Specificity of Adenine-Cu-PO 4 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.