A Facile Metal-Coordinated Spherical Nucleic Acid Nanoplatform for Enhanced Biological Applications by Avoiding Thiol Interference

Spherical nucleic acids (SNAs) have numerous applications in biomedical fields. A traditional SNA was prepared by functionalizing gold nanoparticles (AuNPs) with Au–S bonding. Unfortunately, its practical application was limited, particularly in living cells, due to its susceptibility to cleavage by biothiols and nucleases. To address this issue, we have devised an ultrasimple coordination-driven self-assembly approach to improve the stability and interference resistance of the SNA. The metal-coordinated SNA (SNA@Fe) NP with a homogeneous core–shell structure was achieved through the self-assembly of metal ions and nucleic acids on the surface of an SNA. The nanosystem could enable the encapsulation of chemotherapeutic drugs (SNA@Fe/Drug) in a single step with a high loading efficiency. It also exhibited a significant rise in resistance to biothiols and nucleases, which was essential for the effective transport of nucleic acid and chemotherapeutic agents into cells, so it could perform an enhanced biological role. The metal-coordinated self-assembly interaction provided a straightforward and efficient way to improve the stability of SNAs and had the potential to broaden the application range of SNAs in various biomedical fields.