Research Areas: Bionanotechnology, Biomimetic Surface Science, Biopolymers, Biomaterials, Targeted Drug Delivery, Colloidal Interactions
Targeted Drug Delivery - Currently, the main problems associated with systemic drug administration are the necessity of a large drug dose to achieve high local concentration, non-specific toxicity and other adverse side-effects due to high drug doses, even biodistribution throughout the body and lack of specific affinity for the pathological site. Targeted drug delivery can bring a solution to all these problems. The goal of our biomimetic approach is to engineer vesicles that utilize peptide-amphiphiles to impart targeting functionality, and polyethylene glycol molecules to create a steric barrier to nonspecific interactions and subsequent premature clearance from the blood stream. Our design is based on the idea that a peptide-amphiphile will recognize and specifically bind to the receptor of choice, thus localizing only at sites of inflammation or infection. These studies will provide an insight into the mechanisms by which surface molecules, such as peptide-amphiphiles, modulate vesicle behavior, and will contribute significantly to the rational design and engineering of drug delivery systems with improved targeting functionality and circulation lifetimes.
Peptide Hydrogels for Tissue Engineering - The design of nanofiber scaffolds has been a key objective in tissue engineering as they structurally mimic the natural extracellular matrix (ECM) found in tissues. In an attempt to provide a nanofiber scaffold with a ligand that can promote cell adhesion and ECM production, we propose the use of our peptide-amphiphile nanofibers as a potential scaffold for tissue engineering. The peptide-amphiphiles self assemble into nanofibers in an aqueous environment and form hydrogels. Our goal is to functionalize the hydrogels with various peptide cell binding and growth factor binding domains combined in a modular fashion to produce defined, multicomponent hydrogels, optimized to support the culture and differentiation of different cells, including induced pluripotent stem cells (iPSCs). By optimizing peptide ligand presentation and mechanical properties in the peptide-amphiphile gel system we aim to see improved adhesion, survival and enhanced differentiation efficiency of different cells entrapped in the gel.
- Pearce, T.R., Waybrant, B., and Kokkoli, E. "The Role of Spacers on the Self-Assembly of DNA Aptamer-Amphiphiles into Micelles and Nanotapes", Chem. Commun., 2014, 50 (2): 210 - 212.
- Adil, M., Belur, L., Pearce, T.R., Levine, R.M., Tisdale, A.W., Sorenson, B.S., McIvor, R.S. and Kokkoli, E. "PR_b Functionalized Stealth Liposomes for Targeted Delivery to Metastatic Colon Cancer", Biomater. Sci., 2013, 1 (4): 393-401.
- Waybrant, B., Pearce, T.R., Wang, P., Sreevatsan, S., and Kokkoli, E. "Development and Characterization of an Aptamer Binding Ligand of Fractalkine Using Domain Targeted SELEX", Chem. Comm., 2012, 48 (80): 10043-10045.
- Shroff, K., Rexeisen, E.L., Arunagirinathan, M.A., and Kokkoli, E. "Fibronectin-Mimetic Peptide-Amphiphile Nanofiber Gels Support Increased Cell Adhesion and Promote ECM Production", Soft Matter, 2010, 6 (20): 5064-5072.
- Kokkoli, E., Mardilovich, A., Wedekind, A., Rexeisen, E.L., Garg, A., and Craig, J.A. "Self-Assembly and Applications of Biomimetic and Bioactive Peptide-Amphiphiles", Soft Matter, 2006, 2 (12): 1015-1024.
- Mardilovich, A., Craig, J.A., McCammon, M.Q., Garg, A., and Kokkoli, E. "Design of a Novel Fibronectin-Mimetic Peptide-Amphiphile for Functionalized Biomaterials", Langmuir, 2006, 22 (7): 3259-3264.
- Mardilovich, A., and Kokkoli, E. "Biomimetic Peptide-Amphiphiles for Functional Biomaterials: The Role of GRGDSP and PHSRN", Biomacromolecules, 2004, 5 (3): 950-957.