Targeted drug delivery is an important form of treatment for a variety of diseases, specifically cancers and neurological diseases because it can prevent delivery of treatment to healthy tissue. There are a few challenges associated with current methods of targeted delivery, including disease-specific considerations, where the target tissue is located, and the size and charge of the therapeutic being delivered. Neurological diseases, most specifically those of the central nervous system, are difficult to treat due to the presence of the blood-brain barrier, which protects the central nervous system from harmful chemicals. A variety of approaches have been taken to overcome this problem, one of which is the use of protein-polymer conjugates to connect proteins that target receptors expressed on the target tissue to polymers delivering therapeutics. This allows for an effective way to transgress the blood-brain barrier. Current protein-polymer conjugates have limited ability to functionalize polymers with a variety of molecules, and one of the key polymers used, poly(ethylene) glycol, may have immunogenic effects. Thus, the goal of this project is to synthesize azlactone-functionalized polymers for conjugation to two different protein candidates for targeted drug delivery. To achieve this, we are using poly(2-vinyl-4,4-dimethyl-azlactone) (PVDMA) due to its ability to react with a variety of nucleophilic functional groups that are present in proteins. This polymer will allow us to synthesize diversely functionalized protein-polymer conjugates for drug-delivery applications. This project first has involved the purification and characterization of two different protein-polymer conjugates. Currently, we are functionalizing PVDMA with hydrophilic side chains and conjugating to fibronectin domain proteins (see the image) with lysines at different locations; we have confirmed functionalization using IR spectroscopy and gel electrophoresis. Our next step will be to use cellular assays to assess the efficacy of these new protein-polymer conjugates to target and become internalized by a brain cancer cell line. A poster session deriving from a special studies on a collaborative project between the Moore and Buck Labs, supervised by Alexis Ziemba, Postdoctoral Researcher at Smith College
by Maggie Boyle ‘22 and Yeji Lee ‘22