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.

In this work, an aggregation-induced emission (AIE) molecule (tetraphenylethene derivative, TPE-COOH) was conjugated to elastin-like polypeptides (ELPs40) via an amide bond to form ELPs40-TPE. The successful synthesis of ELPs40-TPE was confirmed by Circular Dichroism spectroscopy, gel electrophoresis, UV-vis absorption, and fluorescence emission spectroscopy. ELPs40-TPE possessed both amphiphilicity and the features of an AIE, and the fluorescence intensity was dependent on the local temperature. The Hela cells imaging indicated that ELPs40-TPE has great potential for bio-imaging applications because of its advantages of high fluorescence intensity, good water-solubility, and remarkable biocompatibility.

A Y-shape and pyrene-modified DNA self-assembly is developed to sensitively and specifically detect microRNA through a pyrene excimer–monomer switch.

DNA-AIEgen hybrids show pH-responsive AIE effects induced by the conformational changes of DNA upon pH variation.

DNA self-assembled fluorescent nanoprobes have been developed for bio-imaging owing to their high resistance to enzyme degradation and great cellular uptake capacity. In this work, we designed a new Y-shaped DNA fluorescent nanoprobe (YFNP) with aggregation-induced emission (AIE) characteristic for microRNA imaging in living cells. With the modification of the AIE dye, the constructed YFNP had a relatively low background fluorescence. However, the YFNP could emit a strong fluorescence due to the generation of microRNA-triggered AIE effect in the presence of target microRNA. Based on the proposed target-triggered emission enhancement strategy, microRNA-21 was detected sensitively and specifically with a detection limit of 122.8 pM. The designed YFNP showed higher bio-stability and cell uptake than the single-stranded DNA fluorescent probe, which has been successfully applied for microRNA imaging in living cells. More importantly, the microRNA-triggered dendrimer structure could be formed after the recognition of target microRNA, achieving a reliable microRNA imaging with a high spatiotemporal resolution. We expect that the proposed YFNP will become a promising candidate for bio-sensing and bio-imaging.

A label- and enzyme-free fluorescence assay based on thioflavin T–induced G-quadruplexes is developed to sensitively and specifically detect telomerase activity. Thioflavin T has a dual role as an efficient inducer and fluorescent probe, and the incorporation of thioflavin T into the thioflavin T–induced G-quadruplexes results in an intense fluorescence enhancement. In the presence of thioflavin T and K+, G-quadruplexes are formed by elongation of the telomerase substrate primer that is catalyzed by telomerase extracted from cancer cells. Thus, the telomerase activity in cancer cell extracts can be evaluated by measuring the thioflavin T fluorescence. More importantly, thioflavin T can specifically recognize and bind to G-quadruplexes, whereas it cannot recognize single- and double-stranded DNAs, which leads to the thioflavin T–based fluorescence assay exhibiting a reduced background and improved signal-to-noise ratio. As a result, the proposed assay has the linear range from 5 to 200 HeLa cells and the detection limit is 34 HeLa cells, which holds great potential for use in the detection of telomerase activity and the diagnosis of cancer.