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Research Projects
In natural systems, self-assembly is used to construct complex, functional systems from simpler components.
For example, the membrane of a mammalian cell is a non-covalent assembly of cholesterol, phospholipids, proteins
and glycoproteins. One of the many cell membrane functions is to initiate a cellular response to subtle changes
in extracellular signals through signal transduction pathways that are initiated upon the binding of a molecule
to a membrane receptor. In recent years, great progress has been made in understanding, predicting, and controlling
self-assembly in synthetic and natural systems. However, the manipulation of assembly processes in biological systems,
and the construction of functional assemblies from simple synthetic components are still challenging problems. The goal
of our research is to utilize and expand current knowledge in supramolecular chemistry for the development of functional
materials that are designed to interface with biological systems.
I. Macromolecular Assemblies as Biomaterials
Recent developments in controlled polymer synthesis, and the imaging of polymeric assemblies provide access
to a wide variety of systems ranging from hydrogels to micelles, worms, vesicles, and nanoparticles.
The properties of these systems can be controlled by the structures of the constituting polymers, and the
conditions under which they are assembled. The potential applications of polymeric assemblies in biology and
medicine are very diverse ranging from the delivery of small molecules, proteins, and DNA in vivo, to their use
as scaffolds for tissue engineering.
To realize the capacity of polymeric assemblies in medical applications, significant progress is still
required to control their behaviour, particularly in vivo under biological conditions. Here we are focusing on
preparing new functional polymers, and using these to make polymer assemblies with controlled biological behaviour.
In addition, we are working on functionalizing polymer assemblies with specific chemical units, either to control their
localization in the body or to facilitate their use as scaffolds for tissue engineering.
II. Contrast Agents for In Vivo Imaging
To realize the capacity of polymeric assemblies in medical applications, significant progress is still required to control their behaviour, particularly in vivo under biological conditions. Here we are focusing on preparing new functional polymers, and using these to make polymer assemblies with controlled biological behaviour. In addition, we are working on functionalizing polymer assemblies with specific chemical units, either to control their localization in the body or to facilitate their use as scaffolds for tissue engineering.
The ongoing development of magnetic resonance imaging (MRI) along with a range of other modalities such as
computed tomography, ultrasound, and optical imaging are essential for the non-invasive diagnosis and study of human
disease. MRI provides high-resolution, three dimensional images of the water distribution within the body, and contrast
agents such as gadolinium complexes provide enhanced contrast against background tissues by catalytically shortening
the relaxation times of nearby water molecules.
In addition to the continuing efforts to improve low molecular weight contrast agents, there has also been significant
interest in the development of macromolecular contrast agents for several reasons. First, macromolecules have very
different biodistribution properties than small molecules, thus facilitating the imaging of distinct biological tissues.
Secondly, due to their multiple functional handles, macromolecules can facilitate the attachment of many contrast
agents (eg. many low molecular weight complexes) to a single targeting group, thus potentially increasing the sensitivity
of targeted imaging. Finally, larger molecules have slower tumbling rates in solution than small molecules, resulting
in increased proton relaxivity and increased signal intensity in the presence of the contrast agent under certain conditions.
Our research in this area focuses on the development of new polymers and polymeric assemblies for the incorporation of
contrast agents. Our goal is to optimize the proton relaxivity and control the in vivo biodistribution properties using
these systems. In addition, by designing multifunctional systems we hope to develop dual imaging agents such as those
capable of providing both magnetic and optical contrast.
IV. Functional Biodegradable Polymers
Biodegradable polymers are of increasing interest for a wide range of applications including tissue engineering, drug delivery, and medical devices. We have been developing biodegradable polymers that degrade by novel mechanisms, potentially allowing for unprecedented control over the degradation rate and for the triggering of polymer degradation under specified conditions. In collaboration with Dr. KIbret Mequanint's group in the Department of Chemical and Biochemical Engineering at the University of Western Ontario we have also been a new class of poly(ester amide)s with pendant functional groups that can be used for the conjugation of drugs or cell signals. These materials are currently being explored for tissue engineering applications.
© F.L.L Nov. 2008. All Rights Reserved.
egillie(at)uwo.ca
Last Updated: Nov 2005