Polyvalent DNA Patches Enable Metal–Organic Fameworks with Enhanced Structural Integrity, Biointerface Stability, and Cellular Uptake

Metal–organic frameworks (MOFs) hold great promise as drug carriers and therapeutic agents in biomedical applications. However, the limited stability of MOF-based carriers in biological environments has garnered increasing attention. Achieving sustained drug release and stability remains a challenge due to the intrinsic instability of MOFs in biological environments. Herein, we report a general postsynthetic modification (PSM) strategy utilizing polyvalent DNA (polyDNA) nanostructures as a universal binder on three representative MOFs. Our findings reveal that the high local density of DNA patches on the MOF surface effectively inhibits competitive ligand-induced linker release and structural collapse. Mechanistic investigations indicate that the cooperative adsorption of adjacent DNA oligos with flexible conformations contributes to enhanced biointerface stability. Importantly, our study demonstrates that polyDNA-modified MOFs exhibit superior stability and enhanced cellular uptake, leading to sustained drug release and improved cytotoxicity against cancer cells. This facile and versatile postsynthesis modification strategy has the potential to advance the application of MOFs in nanomedicine and other fields requiring high structural stability.