A chemically well-defined Bio Core@Inorganic Shell nanohybrid, which consists of rationally designed DNA molecule core with a size of similar to 100 nm and spherical inorganic nanoshell with an overall thickness of similar to 10 nm reassembled with exfoliated layered metal hydroxide (MH nanosheets), is prepared. The DNA encapsulation and its release, due to the pH-dependent solubility of the MH nanoshell, plays a crucial role in maximizing the stability of base sequence-manipulated and probe-functionalized DNA molecules with designed information. The present DNA Core@MH Shell nanohybrid can provide wide bioinspired applications converged with nanotechnology, such as an advanced gene delivery system and a biomedical diagnostics, tracing/collection/sensing system for DNA-based information.