Controlled Delivery of Nitric Oxide Using Porous Organic Cages

In recent years, gas therapy has demonstrated significant potential in the biomedical field. However, existing gas delivery materials often suffer from a limited loading capacity and potential biotoxicity. Porous organic cages (POCs), an emerging subclass of porous materials, offer distinct advantages for gas adsorption and separation due to their intrinsic porosity, solubility, and structural tunability. Herein, we present the first experimental investigation of POCs for nitric oxide (NO) delivery. The tunable molecular design of POCs enables dual adsorption capabilities mechanisms: physisorption and chemisorption via the incorporation of NO-reactive moieties. Through a combination of experimental characterizations and density functional theory calculations, we demonstrated that NO reacts with amine-functionalized POCs to form NONOates, which enables controlled NO release under physiological conditions. High resolution mass spectroscopy provided direct evidence for the process of the formation of NONOates, facilitated by the well-defined and discrete molecular structure of POCs. This work establishes POCs as a promising platform for NO delivery and highlights their broader potential for biomedical applications beyond gas therapy.