The vast majority (>99%) of the injected nanoparticles do not reach their intended destination, which hampers their clinical application. Addressing this problem, the Tanner lab has recently demonstrated that specific choline-based DES can direct preferential accumulation in certain tissues while others can promote transdermal transport or even hitchhike onto blood cells. Considering her unique expertise, REU participants will be tasked with unveiling the role of DES in drug delivery, following the hypothesis that such interactions depend on the chemical properties of the components selected to build the DES. Thus, participants will first synthesize a library of DES based on choline and organic acids ranging in structure, hydrophobicity, and pKa. These DES will be used to coat poly(lactic-co-glycolic) acid nanoparticles, which will be synthesized in-house via nanoprecipitation and solvent evaporation using acetonitrile. Upon characterization (hydrodynamic diameter, zeta potential, and amount of DES adsorbed), participants will investigate their hemocompatibility by RBC hemolysis (incubation at 37°C, centrifugation, and measurement of absorbance at 405 nm). This information will be used to build a database, which will be augmented using RDKit and analyzed using AI models to identify patterns and extract the most significant features controlling hemocompatibility (in collaboration with Garcia’s team). As a result, participants will gain experience in synthesizing DES, characterization methods (including DLS and NMR), and biological methods.