Trinity Strategy: Enabling Perovskite as Hydrophilic and Efficient Fluorescent Nanozyme for Constructing Biomarker Reporting Platform

Water instability and sensing homogeneity are the Achilles’ heel of CsPbX3 NPs in biological fluids application. This work reports the preparation of Mn2+:CsPbCl3@SiO2 yolk–shell nanoparticles (YSNPs) in aqueous solutions created through the integration of ligand, surface, and crystal engineering strategies. The SN2 reaction between 4-chlorobutyric acid (CBA) and oleylamine (OAm) yields a zwitterionic ligand that facilitates the dispersion of YSNPs in water, while the robust SiO2 shell enhances their overall stability. Besides, Mn2+ doping in YSNPs not only introduces a second emission center but also enables potential postsynthetic designability, leading to the switching from YSNPs to MnO2@YSNPs with excellent oxidase (OXD)-like activity. Theoretical calculations reveal that electron transfer from CsPbCl3 to in situ MnO2 and the adsorption–desorption process of 3,3′,5,5′-tetramethylbenzidine (TMB) synergistically amplify the OXD-like activity. In the presence of ascorbic acid (AA), Mn4+ in MnO2@YSNPs (fluorescent nanozyme) is reduced to Mn2+ and dissociated, thereby inhibiting the OXD-like activity and triggering fluorescence “turn-on/off”, i.e., dual-mode recognition. Finally, a biomarker reporting platform based on MnO2@YSNPs fluorescent nanozyme is constructed with AA as the reporter molecule, and the accurate detection of human serum alkaline phosphatase (ALP) is realized, demonstrating the vast potential of perovskites in biosensing.