Ian Corbin, Ph.D., M.Sc.
Ian Corbin, Ph.D., focuses his research on developing innovative approaches to detecting and treating liver cancer. Nanoparticle technology plays a central role in his work. Engineered nanostructures, a thousand times smaller than the diameter of a human hair, are much smaller than a cancer cell and are closer in size to cellular biomolecules such as receptors or enzymes. Because of their small size, these nanoscale devices can readily interact with biomolecules on both the surface and inside cancer cells. By interacting with cancer cells in this manner, nanoparticles have the potential to detect disease and deliver treatments in ways unimagined before now.
Dr. Corbin’s laboratory adopts the unique approach of utilizing the lipoprotein system as a delivery conduit for treating and imaging cancer cells. Lipoproteins are the body’s natural carrier system to transport cholesterol and fat in the blood stream from one cell to another. Once arriving at its destination at a target cell, the lipoprotein particle is internalized and broken down to release its fat cargo to the cells for metabolic and synthetic needs. Cancer cells actively compete with normal cells for lipoproteins, as they need this fat to build membranes while they are actively dividing. By "highjacking" the lipoprotein system Dr. Corbin’s team is able to deliver anti-cancer drugs and imaging agents in a natural and fully biocompatible manner. Their biocompatibility means that lipoprotein particles will circulate below the radar of the immune system and avoid being attacked and eliminated by immune gate-keepers of the body, such as antibodies and macrophage cells. This is a problem many conventional nanoparticles face.
In his current work, Dr. Corbin is isolating natural lipoproteins and modifying them to carry different diagnostic or therapeutic cargos. This modification involves removing the fatty core of the lipoprotein and inducing the lipoprotein to reassemble with a core of hydrophobic imaging probes, or chemotherapy drugs. Alternatively the diagnostic or therapeutic agents can be inserted deep into the surface of the lipoprotein and be transported in this way. However, many times conventional imaging or anticancer agents may not readily associate with lipoproteins. To overcome this hurdle, the researchers attach "oily" molecules such as cholesterol or fatty acids to these agents to aid their integration into the lipoprotein structure.
Although these lipoproteins are modified to contain drugs or detection probes, they are still able to recognize the molecular address of cancer cells, and are rapidly taken up by them. However, while en route in the bloodstream, the lipoprotein nanoparticles may recognize normal cells and also be internalized by them, resulting in toxic adverse effects. To address the toxicity problem Dr. Corbin is also actively investigating strategies for more direct delivery of nanoparticles to cancer. This approach, called local-regional treatment, significantly increases the opportunity for the injected lipoprotein nanoparticles to interact with tumors, and at the same time reduces the exposure of the rest of the body to the nanoparticle. Local-regional treatment is accomplished by either injecting the nanoparticles into the blood vessels directly feeding the tumor, or injecting the nanoparticles into the body cavity or compartment where the tumor is located.
Another approach to specifically targeting cancer cells involves introducing specific homing molecules to the surface of the lipoprotein nanoparticle. Dr. Corbin is also developing methods to attach molecules to the lipoprotein surface that will direct the particle away from its lipoprotein delivery address and re-direct it to an address more specific for cancer. For example, in earlier experiments Dr. Corbin has greatly improved the delivery of his particles to ovarian cancer cells by attaching folic acid molecules to the surface of the lipoprotein nanoparticle.
Besides his lipoprotein work, Dr. Corbin is also exploring the use of other delivery systems, such as liposomes and dendrimer nanostructures, to transport water-soluble drugs and contrast agents to cancer cells. Liposomes are microscopic artificial lipid bubbles that can be loaded with molecular cargo. Dendrimers are large, highly branched spherical molecules that can hold multiple drug molecules. Contrast agents are chemicals that influence MRI-relevant properties of water in tissues to create higher contrast between the tissue and the surrounding water.
For publication information please view Dr. Corbin's faculty profile.