Synthesis of Fluorescein-linked, Zinc-based Metal Organic Frameworks as Carriers of Targeted Treatments for Retinopathies

Metal‐Organic Frameworks (MOFs) are compounds composed of metallic ions linked by organic ligands that form porous units with highly specialized shapes and sizes. Beyond this, MOFs have intrinsic biodegradability, chemical diversity, and a high loading capacity. These characteristics make MOFs optimal candidates as vehicles for drug delivery. More specifically, these programmable, nano‐like particles have the potential to hold specific materials and dissolve in particular environments which makes entrapment and targeted release of various treatments possible. These qualities could be advantageous when treating diseases of the retinal pigment epithelium (RPE). Current treatment involves subretinal injection, which requires a skilled surgeon and often results in retinal detachment and occasional proliferative vitreoretinopathy which leads to acute deterioration of visual facility. MOFs with entrapped treatments can potentially be injected into the vitreous of the eye and targeted to release their payload in the RPE, removing the risk of retinal tearing and the need of a skilled surgeon. To pursue this potential, we modified 4,5‐imidazoledicarboxylic acid (ImDC) ligands with fluorescein via an esterification reaction, while synthesizing MOFs with ImDC. The inclusion of fluorescein will allow for observation of MOF incorporation and processing within the cell. Analysis of the esterified ligand through Gas Chromatography‐Mass Spectroscopy and Nuclear Magnetic Resonance, including homonuclear correlation spectroscopy, indicated that the ligand had been modified. Zinc‐based metal‐organic frameworks with ImDC ligands were synthesized and analyzed by Powder X‐Ray Diffraction to confirm the crystalline structure of the framework. The MOFs were also shown to be partially soluble in potassium chloride and sodium chloride following sonication. Preliminary studies of zinc‐based MOFs in HEK‐293 cells have indicated that the MOFs will likely enter the cells by a phagocytic mechanism. Taken together, these studies will lead to the creation of a system to assess the functionality of MOFs in drug delivery. Future studies will investigate the use of various metals to direct the cellular processing of MOFs. Support or Funding Information Florida Southern College Faculty‐Student Collaborative Research Grant This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .