General and Direct Method for Preparing Oligonucleotide-Functionalized Metal-Organic Framework Nanoparticles

Abstract

Metal-organic frameworks (MOFs) are a class of modular, crystalline, and porous materials that hold promise for storage and transport of chemical cargoes. Though MOFs have been studied in bulk forms, ways of deliberately manipulating the external surface functionality of MOF nanoparticles are less developed. A generalizable approach to modify their surfaces would allow one to impart chemical functionality onto the particle surface that is independent of the bulk MOF structure. Moreover, the use of a chemically programmable ligand, such as DNA, would allow for the manipulation of interparticle interactions. Herein, we report a coordination chemistry-based strategy for the surface functionalization of the external metal nodes of MOF nanoparticles with terminal phosphate-modified oligonucleotides. The external surfaces of nine distinct archetypical MOF particles containing four different metal species (Zr, Cr, Fe, and Al) were successfully functionalized with oligonucleotides, illustrating the generality of this strategy. By taking advantage of the programmable and specific interactions of DNA, 11 distinct MOF particle-inorganic particle core-satellite clusters were synthesized. In these hybrid nanoclusters, the relative stoichiometry, size, shape, and composition of the building blocks can all be independently controlled. This work provides access to a new set of nucleic acid-nanoparticle conjugates, which may be useful as programmable material building blocks and as probes for measuring and manipulating intracellular processes.

Scheme 1. (a) Schematic Representation of Solvothermal Synthesis of UiO-66 MOF Nanoparticles; (b) DNA Modification of MOFs, Utilizing Terminal Phosphate-Modified DNA and Subsequent Sequence-Specific Assembly of MOF-NP Core–Satellite Hybrid architectures

Inset: Zr₆O₄(OH)₄ secondary building units (SBU).

Figure 1

Characterization of DNA functionalized MOF nanoparticles: (a) SEM of UiO-66 and (b) TEM images of DNA functionalized UiO-66. (c) ³¹P{¹H} SSNMR spectra of phosphate functionalized oligonucleotide. Inset: three phosphorus resonances corresponding to unbound phosphodiester (blue), side on Zr bound phosphodiester (gray) and Zr bound terminal phosphate (red). (d) PXRD of simulated UiO-66 (black), 225 nm UiO-66 before (red) and after (blue) DNA functionalization. (e) Melting transition of MOF and 50 nm gold nanoparticle aggregates assembled with complementary DNA. Scale bar = 500 nm in panel a and 2 μm in panel b.

Figure 2

Library of nine MOFs synthesized and further functionalized with DNA. To systematically investigate factors affecting DNA surface coverage, (a) organic linker length, (b) metal node connectivity, and (c) type of metal cluster were independently and deliberately varied and DNA surface coverage was plotted against surface SBU density, SBU coordination number, and M–O bond dissociation energy. Scale bar = 200 nm.

Figure 3

TEM and EDX characterization of DNA interconnected MOF NP-Au NP assemblies. (a) Representative HAADF image of nanoclusters formed from complementary 225 nm DNA-UiO-66 MOF NPs and 20 nm DNA-Au NPs. Inset: schematic illustration of a MOF NP-AuNP cluster, and a single nanocluster. (b) TEM images of nanocluster assemblies demonstrating how the programmable DNA ligands on MOF NPs and AuNPs provide control over the structural makeup of the assemblies (Au NP size and MOF-to-Au NP stoichiometry). All scale bars are 100 nm, except for in panel a, where it is 1 μm.