A Spherical Nucleic Acid Probe Based on the Au-Se Bond

Spherical nucleic acid probes (SNAPs) are 3D nucleic acid nanostructures with multiple superiorities over bare nucleic acid chains. Aubased SNAPs that employ gold nanoparticles (AuNPs) as cores and densely modified nucleic acid chains (commonly via Au-S bonds) as shells have been extensively investigated for the diagnosis and therapy of diverse diseases. However, abundant biothiols in living cells can severely displace nucleic acid chains from AuNPs and restrict their theranostic performance. Herein we report the design and preparation of a selenol terminal-functionalized molecular beacon (MB-SeH), which was further employed to prepare a Au-Se bond-based SNAP (SNAP-Se) for bioimaging. A series of experiments proved the successful preparation of MB-SeH and SNAP-Se, and the obtained nanoprobe could avoid biothiol interference and eliminate the false positive signals during biomarker imaging in living cells. This work will open a new avenue for the design and application of SNAPs.