Construction of Manganese Interpenetrating Amorphous Spherical Nucleic Acids (i‐aSNAs) via Sequential Phase Separation for Robust Nanozymatic Catalysis

ABSTRACT

Amorphous metal nanomaterials (AMNs) are highly coveted catalysts due to their long‐range disordered atomic arrangements and abundant coordinatively unsaturated sites. However, their practical implementation is severely hindered by their inherent thermodynamic drive toward crystallization. Here, we report a DNA condensates‐directed kinetic trapping strategy to construct a new class of hybrid materials termed interpenetrating amorphous spherical nucleic acids (i‐aSNAs). By leveraging a bio‐inspired sequential phase separation pathway, we spatially and temporally regulate manganese metal nucleation within DNA condensates. This process enables DNA to function not merely as a surface ligand, but as a topologically entangled internal scaffold that suppresses atomic rearrangement, coupled with a dense, stabilizing surface layer. The resulting Mn i‐aSNAs exhibit extraordinary oxidase‐like activity with a Michaelis constant ( K _m ) of 16.57 µM, which is a 76.5‐fold enhancement over conventional nanoceria, representing a new benchmark for non‐noble metal nanozymes. Furthermore, this holistic dual‐confinement architecture endows the amorphous phase with robust stability across broad pH and temperature ranges, while maintaining high recyclability. The programmable exposed DNA layer further enables sequence‐specific, target‐mediated catalysis compatible with ELISA‐like assay formats.