Prolonged Circulation of Peptide Amphiphiles for Cancer Imaging
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Series/Report no.:2015 Fall Undergraduate Research Student Poster Forum. 9th
There has been an emerging interest in designing smart, self-assembling, biocompatible materials that can selectively undergo morphological transitions to accumulate at a disease site in response to specific stimuli. One such stimulus is the acidic extracellular pH (6.6-7.0) of tumor tissue. Developing a contrast agent that can self-assemble into a larger, more slowly diffusing entity only in an acidic extracellular pH would enable magnetic resonance imaging (MRI) across all cancers. However, in vivo studies have shown that peptide amphiphiles (PAs) are rapidly cleared by the kidneys and uptaken by the mononuclear phagocyte system. Here, we have characterized the self-assembly of PAs conjugated to polyethylene glycol (PEG) that transition from spherical micelles at the physiological pH 7.4 to cylindrical nanofibers under more acidic pHs. The presence of PEG reduces the ζ-potential of the aggregates and increases the hydrodynamic radius, while increasing micelle formation propensity. The mixing of PEGylated PAs with (DO3A:Gd)-tagged PAs with stronger β-sheet forming region PAs allows for fine-tuning the pH trigger of self-assembly. These findings allow for prolonged-circulation time PA vehicles that transition from spherical micelle to cylindrical nanofiber in simulated serum which could lead to the development of the first pan-cancer MRI contrast agent.
Mathematical and Physical Sciences
Academic Major: Biochemistry
OSU Research Foundation
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