In vitro and in vivo studies of nanomolded PRINT® particles of precisely controlled size, shape, and surface chemistry Public Deposited

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Last Modified
  • March 21, 2019
Creator
  • Gratton, Stephanie E. A.
    • Affiliation: College of Arts and Sciences, Department of Chemistry
Abstract
  • A novel method for the fabrication of polymeric particles on the order of tens of nanometers to several microns is described. This 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 the production of monodisperse, shape-specific nanoparticles from an extensive array of organic precursors. This engineered nature of particle production has a number of advantages over the construction of traditional nanoparticles such as liposomes, dendrimers, and colloidal precipitates. The gentle top down approach of PRINT enables the simultaneous and independent control over particle size and shape, composition, and surface functionality, and permits the loading of delicate cargos such as small organic therapeutics and biological macromolecules. Thus, this single tool serves as a comprehensive platform for the rational design and investigation of new nanocarriers in medicine, having applications ranging from therapeutics to advanced diagnostics. Preliminary in vitro and in vivo studies were conducted, demonstrating the future utility of PRINT particles as delivery vectors in nanomedicine. The interaction of particles with cells is known to be strongly influenced by particle size, however little is known about the interdependent role that size, shape and surface chemistry have on cellular internalization and intracellular trafficking. The internalization of specially-designed, monodisperse hydrogel particles was examined using HeLa cells as a function of size, shape, and surface charge. Evidence of particle internalization was obtained using conventional biological techniques as well as transmission electron microscopy. These findings suggest that HeLa cells readily internalize non-spherical particles with dimensions as large as 3 m 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 non-phagocytic cells.
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  • In Copyright
Advisor
  • DeSimone, Joseph M.
Degree granting institution
  • University of North Carolina at Chapel Hill
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  • Open access
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