The integration of nanomaterials
and nucleic acids has attracted
great attention in various research fields, especially biomedical
applications. Designing two-dimensional nanomaterials and studying
the mechanism of their interaction with nucleic acids are still attractive
tasks. Herein, we designed and prepared a class of ultrathin two-dimensional
metal–organic framework (MOF) nanosheets, named Zr-BTB MOF
nanosheets, composed of Zr–O clusters and 1,3,5-benzenetribenzoate
by a bottom-up synthesis strategy. The Zr-BTB MOF nanosheets possessed
inherent excellent performance such as a high specific surface area,
porosity, and biocompatibility. In addition, we clarified the interaction
difference between the Zr-BTB MOF nanosheets and fluorophore-labeled
double-stranded DNA and single-stranded DNA via molecular dynamics
simulations and fluorescence measurement. Through molecular dynamics
simulations, specific interactions between DNA and nanosheets such
as forces, binding energies, and binding modes were deeply analyzed
and clearly presented. Based on the affinity difference, the system
showed the biosensing potential for target DNA detection with considerable
specificity, sensitivity, and linearity. Our research results presented
the Zr-BTB MOF nanosheet as a platform for nucleic acid detection,
showing the potential for hybridization-based biosensing and related
biological applications.