Applying lithographic techniques from the computer industry to design of new medicines & vaccines; Nanomedicine; Interventional oncology; Fluoropolymers: batteries, microfluidics, minimally adhesive surfaces; Medical devices; Colloid, surfactant and surface chemistry; Role of diversity in innovation; Entrepreneurship from research-intensive universities; Public â€“ private partnerships.
The recent breakthroughs in the DeSimone laboratories using specifically-designed materials for imprint or soft lithography have enabled an extremely versatile and flexible method for the direct fabrication and harvesting of monodisperse, shape-specific nano-biomaterials. The method, referred to as Particle Replication In Non-wetting Templates, or PRINT, allows for the fabrication of 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, stimuli responsive matrices, etc).
In conjunction with the Lineberger Comprehensive Cancer Center, the DeSimone group is focused on designing and evaluating novel nanomedicines for cancer therapy. PRINT nanoparticles can be fabricated into numerous shapes and sizes including nano-cylinders, nano-rods or long filamentous "worm-like" nanoparticles. The unique control over size and shape leads to a variety of nano-materials that can accumulate in specific tissues or diseased sites. Moreover, once the nanoparticle reaches the desired tissue it can be engineered to release a therapeutic at a specific rate and dosage. Techniques that increase the in vivo circulation, and therefore enhance the delivery of a nanoparticle to a tumor are being explored. For example, the surface of a PRINT nanoparticle can be decorated with "stealth" units, which are known to evade routes of elimination. Additionally, by changing the chemical make-up of the nanoparticle, the group can generate an extremely soft and deformable material capable of passing through small pores that exist in tissues like the liver and spleen.
The ability to simultaneously change the size, shape, surface properties and chemical composition of a nanoparticle is unique to the PRINT process. The manipulation of these physical properties can increase the therapeutic index of a drug, reduce side effects and improve patient compliance.
The DeSimone lab is also investigating various routes of administration for PRINT particles. Improved drug delivery to the lung through inhalation represents a promising opportunity for the treatment of many pulmonary and systemic diseases. Through control of particle size, shape and composition, PRINT aerosols offer improved dose uniformity of excipient-free aerosols. With this platform, the DeSimone group is exploring the effect of particle shape on powder entrainment and airway deposition, as well as opportunities for the targeting or de-targeting of airway macrophages.
PRINT particles are being pursued to co-deliver antigens and adjuvants as highly effective particulate vaccines for cancer immunotherapy and treatment of infectious diseases. Micro- and nano-sized particles have shown great promise in vaccine development both as carriers and as particulate adjuvants. PRINT particles with biocompatible materials are designed to efficiently adsorb or incorporate antigens (proteins, peptides, or nucleic acids) and various adjuvants (e.g. TLR ligands). Furthermore, tailoring the surface chemistry, size and shape of PRINT particles may greatly help in the targeting of lymphatic systems to achieve desired immune responses in a cost-effective way.
For over a generation, researchers have utilized suspensions of monodisperse colloids as model systems to address questions concerning the assembly and structure of materials. Suspensions comprised of spherical colloids have long been the system of choice in large part because, until recently, the sphere was one of the few shapes that could be synthesized as monodisperse in large quantities. The recent vision that anisotropically shaped colloids may lead to an entirely new class of materials has caused a paradigm shift in the field. The advent of PRINT places the DeSimone group at the forefront of the colloidal assembly community with the unique ability to synthesize monodisperse colloids with unparalleled control over their shape, size and composition. The DeSimone group is currently using PRINT particles and leveraging fundamental interactions such as depletion, hydrophilic-hydrophobic, etc. to study new physics, create functional materials and produce new colloidal building blocks en route to next-generation materials.
Edward Samulski, PhD; Joel Tepper, MD; Jen Jen Yeh, MD; Richard Stack, MD; Jim Bear, PhD; Mary Napier, PhD; Jeff Frelinger, PhD; Bolyn Hubby, PhD; Ben Maynor, PhD; Jason Rolland, PhD; Neal Fowler; Bill Zamboni, PhD; Valerie Ashby, PhD