Enzyme‐Driven Release of Loads from Nucleic Acid–Capped Metal–Organic Framework Nanoparticles

Abstract Nucleic acid–modified UiO‐68 metal–organic framework nanoparticles, NMOFs, are loaded with the anticancer drug camptothecin (or drug models), and the loaded NMOFs are capped with sequence‐specific duplex units. The NMOFs are unlocked by the biocatalytic decomposition of the duplex capping units that result in the release of the drug (or drug models). The enzymes used are DNase I, a nicking enzyme (Nt.BbvCI), an endonuclease (EcoRI), and an exonuclease III (Exo III). Camptothecin‐loaded NMOFs, capped by tailored hairpin nucleic acids being cooperatively unlocked by adenosine triphosphate (ATP), that is overexpressed in cancer cells, and Exo III are prepared. The camptothecin‐loaded NMOFs reveal that selective cytotoxicity toward MDA‐MB‐231 cancer cells and ≈55% apoptosis of the cancer cells is observed after 5 days of treatment with the NMOFs, while only ≈15% apoptosis of epithelial MCF‐10A breast cells is observed.