Hydrophobic Interaction: A Promising Driving Force for the Biomedical Applications of Nucleic Acids

The comprehensive understanding and proper use of supramolecular interactions have become critical for the development of functional materials, and so is the biomedical application of nucleic acids (NAs). Relatively rare attention has been paid to hydrophobic interaction compared with hydrogen bonding and electrostatic interaction of NAs. However, hydrophobic interaction shows some unique properties, such as high tunability for application interest, minimal effect on NA functionality, and sensitivity to external stimuli. Therefore, the widespread use of hydrophobic interaction has promoted the evolution of NA‐based biomaterials in higher‐order self‐assembly, drug/gene‐delivery systems, and stimuli‐responsive systems. Herein, the recent progress of NA‐based biomaterials whose fabrications or properties are highly determined by hydrophobic interactions is summarized. 1) The hydrophobic interaction of NA itself comes from the accumulation of base‐stacking forces, by which the NAs with certain base compositions and chain lengths show properties similar to thermal‐responsive polymers. 2) In conjugation with hydrophobic molecules, NA amphiphiles show interesting self‐assembly structures with unique properties in many new biosensing and therapeutic strategies. 3) The working‐mechanisms of some NA‐based complex materials are also dependent on hydrophobic interactions. Moreover, in recent attempts, NA amphiphiles have been applied in organizing macroscopic self‐assembly of DNA origami and controlling the cell–cell interactions.