To translate promising molecular discoveries into benefits for patients, we are taking a pharmaco-engineering systems approach to develop the next generation of delivery systems with programmable multi-functional capability. Our laboratory has pioneered the development of a technique called PRINT (Particle Replication in Non-wetting Templates). PRINT is a remarkable top-down particle fabrication technique that has its roots in the manufacturing processes used in the microelectronics industry to make transistors. PRINT is a high resolution molding technique that allows the fabrication of precisely defined nanoparticles with control over size, shape, deformability and surface chemistry. PRINT allows for the precise control over particle size (20 nm to >100 micron), particle shape (spheres, cylinders, discs, toroids), particle composition (organic/inorganic, solid/porous), particle cargo (hydrophilic or hydrophobic therapeutics, biologicals, proteins, oligonucleotides, siRNA, imaging agents such as MR contrast agents, positron emitters), particle modulus (stiff, deformable) and particle surface properties (Avidin/biotin complexes, targeting peptides, antibodies, aptamers, cationic/anion charges, stealth PEG chains). Key therapeutic parameters such as bioavailability, biodistribution, and target-specific cell penetration can be simultaneously designed into a therapy. Extensive in vitro and in vivo studies are focused on fundamental cellular uptake and intracellular trafficking of particles; in vivo biodistribution as a function of size, shape, surface chemistry and deformability; and in vivo tissue and cellular targeting for cancer treatment and diagnosis (PET/CT, MR). In particular, we are using PRINT particles in three areas: i) for the delivery of siRNA; ii) for the targeted delivery of cytotoxins for the fight against cancer; and iii) for the targeting of dendritic cells and T-lymphocytes for the study of autoimmune diseases.