RESEARCH PAPER · Angewandte Chemie · 2026

Metal–Phenolic Coatings Enable Universal Design of Spherical Nucleic Acids

Chaojian Chen, Taokun Luo, Ye Zhang, Xiaowei Liu, Hanwen Zhang, Chad Alexander Mirkin

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Abstract

ABSTRACT Spherical nucleic acids (SNAs), structures consisting of a nanoparticle core chemically modified with a dense shell of nucleic acids, are central to the fields of structural nanomedicine and colloidal crystal engineering with DNA. However, the synthetic methods used to prepare them often require different oligonucleotide immobilization chemistries for each type of core. Here, a general strategy to construct SNAs using metal–phenolic (MP) coatings is introduced. The polymeric shell formed through coordination bonds between polyphenols and metal ions (e.g., Fe 3+ ) can be used to modify the surfaces of a wide variety of particles, spanning a diverse range of sizes, shapes, compositions, and surface charges (e.g., gold spheres and cubes, silica, polystyrene, and melamine resin). Importantly, these shells, regardless of nanoparticle core, can be conjugated to thiolated DNA via Michael addition chemistry. MP‐SNAs retain many of the hallmark properties of conventional SNAs, including enhanced cellular uptake, and serve as versatile building blocks for the programmable assembly of a diverse library of nanoparticles and microparticles into larger and more sophisticated superstructures.

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