(700f) Utilizing UiO-66 Metal-Organic Frameworks (MOFs) As Pulmonary Drug Delivery Vehicles

The pulmonary route is an attractive target for drug delivery applications primarily due to the large surface area of the lung, the noninvasive administration associated with inhaled therapeutics, and the high local drug concentrations for the treatment of respiratory conditions compared to oral or systemic delivery of the same molecule. The recent advances in nanotechnology have revolutionized pulmonary drug delivery by allowing for sustained drug release, controlled deposition, and limited off-target side effects. Metal-organic frameworks (MOFs) have recently emerged as potential drug carriers due to their porous structure, high loading capacity, flexible design, and tunable physiochemical properties. UiO-66, a zirconium and terephthalic acid-based MOF from the University of Oslo series has shown remarkable physical and chemical stability. Here, we examine the use of UiO-66 as a novel pulmonary drug delivery vehicle. Through an acid-free synthesis, we fabricate crystalline UiO-66 particles with tunable defectiveness, (i.e. porosity) which ultimately allows for the control of drug loading and release profiles. The low density and tunable defectiveness afford unique opportunities to control lung penetration and particle deposition. Furthermore, we show that UiO-66 particles have high biocompatibility and low cytotoxicity both in vitro and in vivo. Our results indicate that UiO-66 particles are efficiently internalized by lung innate immune cells, which allows for directed modulation of the lung immune microenvironment and has potential applications in inhaled immunotherapies and nanovaccines. By tuning particle properties, we demonstrate the feasibility of UiO-66 particles as a novel platform for pulmonary drug delivery.