Covalent Organic Framework-Based Spherical Nucleic Acid Probe with a Bonding Defect-Amplified Modification Strategy.

Developing spherical nucleic acids with new structures holds great promise for nanomedicine and bioanalytical fields. Covalent organic frameworks (COFs) are emerging promising materials with unique properties for a wide range of applications. However, devising COF-based spherical nucleic acid is challenging because methods for the preparation of functionalized COFs are still limited. We report here a bonding defect-amplified modification (BDAM) strategy for the facile preparation of functionalized COFs. Poly(acrylic acid) was employed as the defect amplifier to modify the surface of COF nanoparticles by the formation of amide bonds with amino residues, which successfully converted and amplified the residues into abundant reactive carboxyl groups. Then, amino terminal-decorated hairpin DNA was densely grafted onto the surface of COF nanoparticles (NPs) to give rise to a spherical nucleic acid probe (SNAP). A series of experiments and characterizations proved the successful preparation of the COF-based SNAP, and its application in specifically lighting up RNA biomarkers in living cells for cancer diagnostic imaging was demonstrated. Therefore, the COF-based SNAP is a promising candidate for biomedical applications and the proposed BDAM represents a useful strategy for the preparation of functionalized COFs for diverse fields.