1) We are making a library of amino-retinoid compounds from the reaction of all-trans-retinal and a series of biogenic amines (figs. 1 & 2). The resulting retinoid adducts are then subjected to chemical and photochemical oxidation. These compounds will be used as standards in the isolation project described below (2) and will serve as substrates for use in targeted and triggered drug delivery cancer therapies (section 3).

     2) All-trans-retinal reacts with phosphatidyl ethanolamine in the ROS of the eye (retina) to form A2E, a compound implicated in the cause of AMD. All-trans-retinal may also be reacting with other biogenic amines found in the retina, particularly in ROS. Compounds from our retinoid library (section 1) are being used as standards for detection of these compounds in human and mouse RPE extracts. We have found HPLC peaks associated with novel amino-retinoid compounds and are in the process of characterizing them.

     3) A third project that we are developing is the targeted and triggered drug delivery of oxidized amino-retinoid compounds for use in cancer therapy. Compounds, such as A2E, form oxidation products upon irradiation, which are more cytotoxic than the original unoxidized compound. We have found that unoxidized A2E is non-toxic in HeLa and HL-60 cells and is cytotoxic after irradiation with blue light. We have attached folic acid to A2E which is upregulated in selected cancer cells and will thus target these cells over normal cells. All amino-retinoid compounds in library will be screened, and compounds with little cytotoxicity in the unoxidized form and increased cytotoxicity after oxidation will be developed for applications in targeted and triggered drug delivery therapies.