Accurate assembly and direct characterization of DNA nanogels crosslinked by G-quadruplex, i-motif and duplex with surface-enhanced Raman spectroscopy.

The direct characterization of DNA nanogels at the atomic level is desirable and of great significance, however, has been challenging because of structural complexity and the larger size of nanogels. Herein, we demonstrated a simple, sensitive and reliable SERS (Surface-enhanced Raman spectroscopy)-based approach towards direct monitoring microstructures, such as three types of nanogels crosslinked by DNA G-quadruplex, i-motif and GC duplex. The achievement is attributed to the detection of featured Raman bands corresponding to the formation of Watson-Crick and Hoogsteen hydrogen bonds as well as C·C+ base pairs. Importantly, this work reveals that the silver nanoparticles attaching on the surface of nanogels can form local 'hotspots' and produce high-quality of Raman spectra under the assistance of iodide, aluminum ions and dichloromethane, therefore, shows great potential for wide applications in accurate characterization of various DNA nanostructures.