Engineering Programmable DNA Particles and Capsules Using Catechol-Functionalized DNA Block Copolymers

DNA block copolymer (DBC) assemblies have attracted attention because of their tunable properties (e.g., programmability, high biocompatibility, efficient cellular uptake, and stability against enzymatic degradation); however, controlling the size of DNA block copolymer assemblies and preparing well-defined DNA-functionalized particle systems are challenging. Herein, we report the preparation of DBC-based particles and capsules with different sizes (i.e., from approximately 0.15 to 3.2 μm) and a narrow size distribution (i.e., polydispersity index <0.2) through the assembly of catechol-functionalized DBC, DNA-b-poly(methyl methacrylate-co-2-methacryloylethyl dihydrocaffeate, with metal ions (e.g., Fe^III). This assembly process largely exploits the coordination bonding of the metal ions and phenolic (i.e., catechol) groups, forming metal-phenolic networks (MPNs). The DBC-Fe^IIIMPN capsules formed are stable under acidic, metal-chelating, and surfactant solutions because of the coexistence of metal coordination, hydrogen bonding, and hydrophobic interactions. The molecular recognition properties of the DNA strands enable tailorable interactions with small molecules and nanoparticles and are used to tune the permeability of the assembled capsules (>40% permeability decrease for 2000 kDa fluorescein isothiocyanate dextran compared with untreated capsules). The DBC-Fe^IIIMPN particles show efficient cellular uptake and endosomal escape capability, allowing the efficient delivery of small-interfering RNA for gene silencing (89% downregulation). The reported approach provides the rational design of a range of DNA-functionalized particles, which can potentially be applied in materials science and biomedical applications.