Stephanie E. A. Gratton

The effect of particle design on cellular internalization pathways

The interaction of particles with cells is known to be strongly influenced by particle size, but little is known about the interdependent role that size, shape, and surface chemistry have on cellular internalization and intracellular trafficking. We report on the internalization of specially designed, monodisperse hydrogel particles into HeLa cells as a function of size, shape, and surface charge. We employ a top-down particle fabrication technique called PRINT that is able to generate uniform populations of organic micro- and nanoparticles with complete control of size, shape, and surface chemistry. Evidence of particle internalization was obtained by using conventional biological techniques and transmission electron microscopy. These findings suggest that HeLa cells readily internalize nonspherical particles with dimensions as large as 3 μm by using several different mechanisms of endocytosis. Moreover, it was found that rod-like particles enjoy an appreciable advantage when it comes to internalization rates, reminiscent of the advantage that many rod-like bacteria have for internalization in nonphagocytic cells.

Fabrication of multiphasic and regio-specifically functionalized PRINT ® particles of controlled size and shape

Using Particle Replication In Nonwetting Templates (PRINT ® ) technology, multiphasic and regio-specifically functionalized shape-controlled particles have been fabricated that include end-labeled particles via post- functionalization; biphasic Janus particles that integrate two compositionally different chemistries into a single particle; and more complex multiphasic shape-specific particles. Controlling the anisotropic distribution of matter within a particle creates an extra parameter in the colloidal particle design, providing opportunities to generate advanced particles with versatile and tunable compositions, properties, and thus functionalities. Owing to their robust characteristics, these multiphasic and regio-specifically functionalized PRINT particles should be promising platforms for applications in life science and materials science.

Monodisperse nanocarriers: novel fabrication of polymeric nanoparticles for bio-nanotechnology

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.

Role of surface chemistry and topology of chemoselectively tailored embossed films on shear adhesion

Surface topology has been shown to play a crucial role in the adhesive ability of gecko-inspired, embossed films. Herein, we report the use of Pattern Replication In Non-wetting Templates (PRINT) to design micro- and nano-embossed films in order to explore the relationship between surface chemistry, feature size, feature geometry, and shear adhesion. Ketone-containing elastomers were synthesized from various amounts of poly(ethylene glycol) diacrylate, 2-hydroxyethyl methacrylate, and 2-(methacryloyloxy)ethyl acetoacetate. Due to the presence of the ketone, elastomer functionalization was demonstrated with various oxyamine-, hydrazine-, and hydrazide-terminated ligands. Films were also shown to be non-cytotoxic for future applications in biomedically related fields. This system may allow for the design of flexible adhesives that can be selectively tailored for a range of applications.