Publication Date

Spring 2011

Document Type

Project Summary

Degree Name

Master of Science

Department

Analytical Chemistry

First Advisor

Walter Henne, Jr., Ph.D.

Second Advisor

Patty Fu-Giles, Ph.D.

Third Advisor

Stephen Kent, M.B.A.

Abstract

Folate receptors have two glycosyl phosphatidylinositol anchored isomers, alpha and beta. Folate receptor alpha binds with high affinity for folic acid and act as a receptor for mediated transport of folate into the cells. Folate is necessary for DNA metabolism and thus it is speculated that rapidly dividing cancer cells have an increased necessity for folic acid. Folate receptor alpha levels eminent in specific malignant diseases (like solid tumors and leukemia) and thus folate receptors serve in the detection of FR+ (Folate receptor positive) and diagnosis of cancers.

In general, liposomes have the capacity intake the most imaging and toxic agents due to their large diameter size (100nm). In the liposomal system, the most important thing for therapeutic activity is the conjugation between the liposome and folic acid due to the:

  1. Need to present folate to the cancer cell surface unfettered from the bulky liposome (in order to bind to the folate surface).
  2. Need to have sufficient folate ligands for proficient binding to cell but not much more folate molecules that could result in non-specific binding.

In the liposomal system, folate is attached to poly ethylene glycol (PEG), which is incorporated into the lipid membrane by way of a hydrophobic tail. Although widely established, liposomes require a fair degree of technical ability to synthesize and analyze. Recently, it has been revealed that apoferritin (iron transport protein), 450 kD polymeric protein (at 70 nm in diameter), is capable of being dissociated into its respective subunits at low pH 2 and re-associated at pH around 8.5 to restructure the apoferritin cage for therapeutic purposes. Based on all these results, our project aim is to synthesize a folate based apoferritin probe. The type of folate conjugation to the apoferritin, the degree of folate labeling to the protein, the quantity of dye incorporation into the protein cage and type of dye, drugs and other agents will be assessed and ultimately be tested for cell uptake. These types of cages are useful for the production of radio-imaging agents, MRI contrast agents and some drug delivery systems. The main goal of this project is to make an economical and easily produced folate probe that will be substituted for more costly and cumbersome liposome delivery vehicles.

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