Facile synthesis of tunable zinc–adenine frameworks for aptamer-based biological applications

Abstract

Zinc-based metal–organic frameworks (ZnMOFs) have attracted significant attention in bioanalytical and biomedical applications owing to their structural tunability, biocompatibility, and potential for integration with molecular recognition elements. In this study, we report a facile aqueous synthesis of ZnMOFs using adenine as a nucleobase linker and explore their multifunctionality for aptamer-based biological applications. Density functional theory calculations revealed Zn–N coordination and Zn–cluster formation underpinning the inherently amorphous framework architecture. The resulting amorphous ZnMOF particles exhibited a controllable size and tunable surface charge through post-synthesis treatments such as polystyrene sulfonate treatment and sonication. Notably, the system enables direct incorporation of aptamers via their poly-adenine tails without post-synthesis biofunctionalization steps. Incorporation of ZnMOFs with a VCAM-1 aptamer enhanced fluorescence signals in the immunofluorescence assay and flow cytometry, providing a sensitive platform for biomolecular detection. Additionally, ZnMOFs decorated with a CD63 aptamer enabled selective exosome capture with gentle recovery, maintaining the biomarker's integrity for downstream quantitative reverse transcriptase loop-mediated isothermal amplification (qRT-LAMP) of exosomal RNA. Collectively, our findings establish ZnMOFs as simple, versatile, and tunable platforms for aptamer-based sensing and exosome isolation, with broad potential for biological and biomedical applications.