We report here on the design of inorganic–organic hybrid materials, which consist of layered double hydroxides (LDHs) as inorganic carrier and short single-stranded nucleic acids (ssDNA) as organic molecules. LDHs were prepared by the co-precipitation method followed by hydrothermal treatment. A model 12-nucleotide-long sequence was immobilized either by ion exchange or covalent grafting. Both the LDH composition and the nucleic acid-to-particle ratio were optimized throughout the synthesis to develop highly stable suspensions of the hybrid materials. Structural characterization revealed that the covalent attachment of the ssDNA was successfully achieved via silanization of the LDHs in aqueous suspension. Covalent linkage of the nucleic acids confers to this model nanoparticulate system promising properties and potential for applications as therapeutic agents. Fragments of nucleic acids could be introduced into living cells without release during the delivery process since LDHs slowly dissolve in the slightly acidic intracellular space.