DNA adsorption on nanoscale zeolitic imidazolate framework-8 enabling rational design of a DNA-based nanoprobe for gene detection and regulation in living cells

Abstract

DNA functionalized nanomaterials have attracted tremendous attention for bioanalytical applications. Owing to exceptional fluorescence quenching ability, most DNA-based nanoprobes were designed with turn-on signals for target gene detection, while only a few of them could simultaneously achieve gene detection and regulation in one system. In this study, we explored the use of nanoscale zeolitic imidazolate framework-8 (ZIF-8) as a building block to construct a DNA-based nanoprobe. We found ZIF-8 could stably adsorb DNA to resist the dissociation by various biological ligands, enabling potential biological applications. However, ZIF-8 was not a nano-quencher to turn off the fluorophore labeling on the adsorbed DNA. We therefore designed a DNAzyme embedded molecular beacon (DMB) to functionalize ZIF-8. After endocytosis, ZIF-8 was disintegrated to release DMB for target mRNA detection, and the co-released Zn²⁺ acted as an effective cofactor to activate the embedded DNAzyme for mRNA regulation. This study provides a versatile nano-platform to realize multiple functions inside cells by using functional nucleic acids, which holds great promise for theranostic applications.