Abstract 2648: Top-down nanofabrication techniques applied to the design of engineered drug therapies
Authors: Napier Mary , DeSimone Joseph , Luft Chris , Conwell Christine , Chang Kelly 
Published: February 2011

A novel method for the fabrication of organic particles on the order of tens of nanometers to several microns will be described. Our imprint lithographic technique called PRINT® (Particle Replication In Non-wetting Templates), takes advantage of the unique properties of elastomeric molds comprised of a low surface energy perfluoropolyether network, allowing for the production of monodisperse, shape-specific particles from an extensive array of organic precursors. The engineered nature of particle production has a number of advantages over the fabrication of traditional nanoparticles such as liposomes, dendrimers, and colloidal precipitates. The nature of PRINT technology takes drug delivery into the uncharted realm of engineered drug therapies given its á la carte approach and versatility. PRINT allows for the precise control over particle size, shape, composition, cargo, modulus and surface properties with the ability to independently design these attributes to create truly engineered drug therapies.

For the first time, key therapeutic parameters such as bioavailability, biodistribution, and target-specific cell penetration can be simultaneously designed into a therapy or imaging agent. Preliminary in vitro and in vivo studies are being conducted to demonstrate the promise of PRINT particles as delivery vectors and novel imaging agents for the treatment of disease. Cellular uptake of PRINT particles is strongly influenced by the size, shape, charge and targeting ligand. The HeLa cell line (human epithelial) was employed to investigate the uptake of cubic, cylindrical particles and high aspect ratio worm-like particles with a range of sizes and surface chemistries with fluoroscein-isothiocynate (FITC) added as a tracking agent. These findings suggest that cellular internalization of particles exhibited a strong dependence on physical parameters. Understanding the parameters for cellular uptake will aid us in designing particles that will perform and function as required by the application. PRINT particles have been decorated with a variety of targeting ligands for targeted delivery of therapeutics or imaging agents in vivo. The targeting ligands have included monoclonal antibodies to the transferrin and folate α receptors, herceptin, Her2/neu and the binding and internalization studied on a variety of cancer and control cell lines. Biodistribution of nanoparticles of varying size and surface functionalities in both healthy and tumor-bearing mice models are also being examined. Two modalities are used to track the PRINT particles in vivo; a static profile using a fluorescent label and a dynamic PET profile obtained using 64Cu labeled particles. Knowing where the PRINT particles travel in vivo forms the foundation for development of effective drug delivery vectors. The knowledge garnered from these studies will be used in the development of novel particle based chemotherapeutic and imaging agents.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 2648.