Nucleic acid strands can be synthesized into various nucleic acid-based nanomaterials (NANs) through strict
base pairing. The self-assembled NANs are programmable, intelligent, biocompatible, non-immunogenic, and noncytotoxic. With the rapid development of nanotechnology, the application of NANs in the biomedical fields, such as
drug delivery and biological sensing, has attracted wide attention. However, the stability of NANs is often affected by
the cation concentrations, enzymatic degradation, and organic solvents. This susceptibility to degradation is one of the
most important factors that have restricted the application of NANs. NANs can be denatured or degraded under conditions of low cation concentrations, enzymatic presence, and organic solvents. To deal with this issue, a lot of methods
have been attempted to improve the stability of NANs, including artificial nucleic acids, modification with specific
groups, encapsulation with protective structures, etc. In this review, we summarized the relevant methods to have a
deeper understanding of the stability of NANs.