The delivery of therapeutic, detection and imaging agents for the diagnosis and treatment of cancer patients has improved dramatically over the years with the development of nano-carriers such as liposomes, micelles, dendrimers, biomolecules, polymer particles, and colloidal precipitates. While many of these carriers have been used with great success in vitro and in vivo, each suffers from serious drawbacks with regard to stability, flexibility, or functionality. To date, there has been no general particle fabrication method available that afforded rigorous control over particle size, shape, composition, cargo and chemical structure. By utilizing the method we has designed referred to as Particle Replication In Non-wetting Templates, or PRINT, we can fabricate monodisperse particles with simultaneous control over structure (i.e. shape, size, composition) and function (i.e. cargo, surface structure). Unlike other particle fabrication techniques, PRINT is delicate and general enough to be compatible with a variety of important next-generation cancer therapeutic, detection and imaging agents, including various cargos (e.g. DNA, proteins, chemotherapy drugs, biosensor dyes, radio-markers, contrast agents), targeting ligands (e.g. antibodies, cell targeting peptides) and functional matrix materials (e.g. bioabsorbable polymers or stimuli responsive matrices). PRINT makes this possible by utilizing low-surface energy, chemically resistant fluoropolymers as molding materials and patterned substrates to produce functional, harvestable, monodisperse polymeric particles.
By using PRINT (Particle Replication In Non-wetting Templates), a general soft technique for replication of diverse shapes at the sub-micron level, we have been able to produce organic nano-particles. Lithographic patterning (using 193nm exposure tool) was employed to generate 160nm posts on a 6" Si wafer; the material of the posts being the organic polymer based commercial photoresist. RIE was then performed on the patterned substrate to transfer the geometry to the Si; various aspect ratios of the Si nano-posts were obtained upon etch time variation. PRINT was used to make a mold of the nano-features on the Si wafer and subsequently fabricate cross-linked organic nano-particles by using PEG-diacrylate (PolyEthylene Glycol diacrylate). Such organic nano-matrices would be potentially useful as therapeutic agent carriers, imaging chemical encapsulants and localized drug delivery vehicles.