Imparting Designer Biorecognition Functionality to Metal–Organic Frameworks by a DNA‐Mediated Surface Engineering Strategy

Surface functionality is an essential component for processing and application of metal–organic frameworks (MOFs). A simple and cost‐effective strategy for DNA‐mediated surface engineering of zirconium‐based nanoscale MOFs (NMOFs) is presented, capable of endowing them with specific molecular recognition properties and thus expanding their potential for applications in nanotechnology and biotechnology. It is shown that efficient immobilization of functional DNA on NMOFs can be achieved via surface coordination chemistry. With this strategy, it is demonstrated that such porphyrin‐based NMOFs can be modified with a DNA aptamer for targeting specific cancer cells. Furthermore, the DNA–NMOFs can facilitate the delivery of therapeutic DNA (e.g., CpG) into cells for efficient recognition of endosomal Toll‐like receptor 9 and subsequent enhanced immunostimulatory activity in vitro and in vivo. No apparent toxicity is observed with systemic delivery of the DNA–NMOFs in vivo. Overall, these results suggest that the strategy allows for surface functionalization of MOFs with different functional DNAs, extending the use of these materials to diverse applications in biosensor, bioimaging, and nanomedicine.