15D13 Biomolecular Engineering

Supramolecular Micellar Assemblies for Molecular Targeting of Cardiovascular Disease and Cancer

Eun Ji Chung, Laurie B. Drews, Kathryn Nord, and Matthew Tirrell
Cardiovascular disease and cancer are the leading causes of morbidity and mortality in the US and worldwide. In order to more accurately diagnose and locally deliver a therapy, we have designed and incorporated molecular targets to peptide amphiphiles micelles (PAMs). Peptide amphiphiles (PAs) are a class of synthetic molecules in which a biologically active peptide â??headgroupâ? is chemically linked to a hydrophobic â??tailâ?. Under aqueous conditions, the PAs self-assemble into micelles in which the tails form the core, sequestered from water, and the peptides are displayed in the micellar corona on the exterior. Micelles formed from PAs are advantageous because a locally concentrated, multivalent display of a peptide can be used to potentiate binding to a disease target of interest. Furthermore, the nanometer size provides favorable pharmacokinetic properties in vivo. Interestingly, recent microarray data confirmed the biomimetic properties of PAMs and their ability to recapitulate biological properties of the native protein.
When the fibrin-targeting peptide, cysteine-arginine-gluatamic acid-lysine-alanine (CREKA, previously identified via in vivo phage display), was used as the headgroup, these PAMs localized intravascularly in the mouse model of glioblastoma, or primary brain tumors that account for 70% of all malignant gliomas. Moreover, upon incorporation of the receptor binding motif of monocyte chemoattractant protein-1 (MCP-1), MCP-1 PAMs localized to monocytes found on atherosclerotic plaques and accumulated with the progression of the disease in vivo. All micelles were found to be biocompatible and cleared via the renal and mononuclear phagocyte systems. Since PAMs can be synthesized with multiple functionalities (i.e. targeting element, imaging dye, therapeutic, etc.) and the hydrophobic core can be exploited for drug delivery, we are exploring the efficacy of PAM-mediated, local drug delivery. This work, coupled with investigations incorporating various imaging agents that are used currently in the clinic, has the potential to provide a molecular imaging tool that can bind to specific markers of interest, deliver a therapeutic, and monitor the regression of the disease in real-time.
Dear Session Chairs, I just wanted to let you know that I will be attending this year's AIChE as a faculty candidate and would appreciate any attention that you could bring to this session. Thank you. Eun Ji Chung