Peptide Amphiphile MRI Contrast Agent Relaxivity and Self-Assembly Behavior
Loading...
Date
2016-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
There has been an emerging interest in designing novel, biocompatible materials that can selectively undergo morphological transitions to accumulate at a cancer site in response to specific stimuli. One such stimulus is the acidic extracellular pH (6.6–7.0) of tumor tissue. Developing a magnetic resonance imaging (MRI) contrast agent that can self-assemble into a larger, more slowly diffusing entity only in the acidic extracellular pH would provide sufficient accumulation at the tumor site to allow it to selectively target all cancers and increase MRI resolution about the disease site. There is a significant challenge in achieving such a transition in vivo without understanding how the contrast agent structure can affect the self-assembly process. Here, we characterize the tunable self-assembling behavior of six peptide amphiphiles (PAs) from spherical micelles at higher pHs to cylindrical nanofibers at lower pHs. The molecular structure of each PA varies in the hydrophobic core, β-sheet forming, or charged region to assess how these changes affect self-assembly. The morphological pH and concentration dependence of the PAs was monitored in an isotonic salt solution mimicking that of blood serum using Critical Aggregation Concentration measurements and Circular Dichroism Spectroscopy. Moreover, the T1 Relaxivity of the PAs was obtained to observe how morphological changes affect relaxation rates. It was found that increasing the length of the alkyl-tail, increasing the relative strength of the β-sheet forming region, and decreasing the relative strength of the charged region all function to increase the pH of transition, and vice-versa. These results provide a framework for optimizing PA structure to create a novel, pan-cancer, increased-resolution MRI contrast agent.
Description
Keywords
Peptide, self-assembly, nanofiber, micelle, relaxivity