Molecularly pure miktoarm spherical nucleic acids: preparation and usage as a scaffold for abiotic intracellular catalysis

We present a fullerene-based strategy that allows the synthesis of molecularly pure miktoarm spherical nucleic acids (SNAs) with diverse structures, which, with post-functionalization, could serve as efficient scaffolds for intracellular catalysis. The SNA structure promotes cell permeability, nucleic acid stability, and catalytic efficiency, making the platform ideal for in cellulo reactions. Consequently, the tris(triazole)-bearing miktoarm SNA was able to effectively mediate intracellular copper-catalyzed alkyne-azide cycloaddition at nanomolar level of copper, and facilitate the same reaction in live zebrafish. Biocompatible nano-constructs, with definite molecular structures and programmable subunits, can potentially be used as biocatalysts with modular functional moieties.