The Creation of PEGylated pH-Triggered Self-Assembling Peptide Amphiphiles for Long-Circulating Cancer Targeting MRI Contrast Agents
Loading...
Date
2017-05
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
The Ohio State University
Abstract
To date there is no Magnetic Resonance Imaging (MRI) contrast agent that selectively targets cancer, despite it being the highest resolution diagnostic technique. The challenge lies with designing a biocompatible FDA- approvable contrast agent that can locally accumulate only in the extracellular environment of tumor tissue at a 10 μM concentration. To accumulate an imaging agent selectively in the tumor tissue we have established a new class of self-assembling vehicles that circulate through the body as 10 nm spherical micelles and transition into slowly diffusing μm-long fibers upon entering the acidic extracellular vasculature of tumor tissue. However, to maximize accumulation, it is essential to maximize the amount of time that these vehicles circulate through the blood stream before they are cleared by the immune system. The addition of a polyethylene glycol (PEG) shell to circulating vehicles is a well-established method for minimizing an immune response, and allowing long circulation. However, incorporating this PEG shell onto these transitioning peptide amphiphile (PA) vehicles impacts their self-assembly behavior. Here, we have established the influence of PEG on the transitioning properties of these PAs through the characterization of the pH – concentration phase diagrams of different mixtures of 2000 kDa PEGylated and unPEGylated PAs. We show that PEG termination disrupts self-assembly, resulting in an increased critical micelle concentration and a more acidic nanofiber to micelle transition. PAs that have greater propensity to form nanofibers need more relative amounts of PEGylated PAs to maintain a transition at a uniform pH. In conclusion, we show that it is indeed possible to create a PEGylated vehicle that transitions in a serum environment at a pH of 7, which will enable the creation of a long-circulating transitioning MRI contrast agent.
Description
Keywords
Self-Assembly, peptide amphiphiles, stimuli-responsive, MRI, cancer imaging