Project 1

Development of ‘Smart’ Nanoparticles
for Cancer Therapy and Imaging

Joseph DeSimone, Ph.D.

Kenan Professor of Chemistry and Chemical Engineering, Project PI

Project 1 is based on the PRINT (Particle Replication In Non-wetting Templates) technology for nanoparticle fabrication recently developed in the DeSimone laboratory. This process, called “soft” or “non-wetting” imprint lithography, involves first the creation of the desired shape in a silicon template using electron beam lithography. A mold is made of this template using novel liquid fluoropolymers that can be polymerized into a Teflon-like solid. The mold can then be filled with any desired polymerizable material. After polymerization, the contents of the mold are extruded. PRINT technology allows the generation of completely isolated nanostructures of virtually any size and shape by taking advantage of the inherently low surface energy and swelling resistance of photocurable perfluoropolyethers (PFPEs).

PRINT technology allows precise control of nanoparticle size and shape. It is also very flexible in that a variety of polymerizable materials and additives can be used, since the geometry of the particle is controlled only by the mold and is not affected by the chemical composition. Thus the nanoparticles can be comprised of biodegradable materials, can include substances such as PEG to ‘passivate’ the surface and promote long lifetimes in the circulation, and can include amino or sulfhydryl groups that will facilitate the linkage of peptides or oligonucleotides to the nanoparticle surface.

Nanoparticles fabricated using the PRINT technology will be developed as carriers of conventional antitumor drugs, antisense and siRNA oligonucleotides, and X-ray or MRI contrast agents. The nanoparticles will be rendered ‘smart, by conjugating their surfaces with peptides or nucleic acid aptamers directed at receptors found on tumor cells or on tumor vasculature. Many of these targeting reagents will be provided by the Combinatorial Library Research Core.


The Aims of Project 1 include:

  • scaling up the PRINT technology to allow nanoparticle production on the gram scale
  • preparing biodegradable nanoparticles of varying size (20-200 nm) shape and composition
  • testing the stability and release profiles of nanoparticles containing drugs, oligonucleotides, or imaging agents
  • testing the blood clearance kinetics and biodistribution of nanoparticles of varying size and shape in normal and tumor bearing mice (this will make use of the Pharmacokinetics, Biodistribution, and Biocompatibility Core, Animal Models Core, and the Small Animal Imaging Core). Project 1 will provide materials for Project 2 (applications of nanoparticles) and in turn will receive feedback from Project 2. Project 1 will also interface with Project 4 regarding use of magnetic nanomaterials.


The Nanoparticle Foundry. We anticipate that Project 1 will not only be a key component of the UNC CCNE, but will also be a national resource for the design, fabrication, and testing of a variety of nanoparticles for cancer diagnosis and therapy. The ‘Foundry’ will interact with other CCNEs to meet their needs for nanoparticles as tools for basic and translational research.

Links:

Professor DeSimone's home page

NSF Science and Technology Center for Environmentally Responsible Solvents and Processes
 
 
 
 
 
 
 
 
 
 
 
 
 
 
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