Electrophoretic Disruption of Nonspecific Peptide Interactions with MMP-Sensitive Hydrogels

Y. Zhang1 and R. A. Gemeinhart1

1University of Illinois, Chicago, IL 60612-7213 USA

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Summary
Matrix metalloproteases (MMPs) overexpression plays a critical role in cancer invasion and metastasis. We utilized this key feature of tumor microenvironment to develop a disease-stimuli triggered drug delivery system. Although there were significantly more peptides released in the presence of MMP-2 compared with the control groups, we sought improved methods for removing unreacted peptide and to understand why the peptides were so well retained. A novel method of electrophoretic washing was developed disrupting the strong electrostatic interactions between the peptides and the pendant groups of the hydrogel. After electrophoresis, the nonspecific peptide release in the absence of MMP-2 was minimized. This newly developed purification system significantly improved the control of release to be in response of the magnitude of the stimuli, i.e. MMP. Specifically, peptides were released proportionally to the concentration of MMP-2 present. Now that many of the design parameters have been examined, anticancer drugs will be conjugated to the MMP sensitive peptide linkers with the goal of implantion in a tumor void releasing anticancer reagent in response to elevated level of MMPs.

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