Loading...
Synthesis of pH-responsive polymers via RAFT polymerization and their use for preparation of pH-responsive MRI contrast agents
Zhu, Liping
Zhu, Liping
Citations
Altmetric:
Advisor
Editor
Date
Date Issued
2015
Date Submitted
Collections
Research Projects
Organizational Units
Journal Issue
Embargo Expires
2015-08-01
Abstract
Despite recent advances in the understanding of fundamental cancer biology, cancer remains the second most common cause of death in the United States. One of the primary factors indicative of high cancer morbidity and mortality and aggressive cancer phenotypes is tumors with a low extracellular pH (pHe). Thus, the ability to measure tumor pHe in vivo using non-invasive and accurate techniques that also provide high spatiotemporal resolution has become increasingly important and is of great interest to both researchers and clinicians. Recently, the use of pH-responsive polymer systems in cancer diagnostics and treatment has received considerable attention due to their ability to undergo conformational changes in response to changes in the environmental pH. We have developed pH-responsive nanoscale contrast agents based on pH-responsive polymers and gadolinium (Gd) based nanoparticles for magnetic resonance imaging (MRI) that demonstrate large changes in relaxivity to improve both the selectivity and sensitivity of in vivo pHe measurement. A series of pH-responsive biocompatible block polymers with pKa ranging from 5.0 to 7.0 have been synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization. In this research, we chose three tertiary amine based methacrylates, including 2-(diisopropylamino)ethyl methacrylate (DPAEMA), 2-(dibutylamino)ethyl methacrylate (DBAEMA), and 2-(piperidino)ethyl methacrylate (PPDEMA), to prepare their homopolymers and block copolymers with poly(ethylene glycol) (PEG) maro-RAFT agents via RAFT polymerizations and studied the polymerization kinetics of both. The pH-responsive properties of these block copolymers also has been studied through pKa titration and calculation, dynamic light scattering. These copolymers have then been used to modify Gd-based nanoparticles (GdNPs) via a grafting to method after reduction of the thiocarbonylthio end groups under basic conditions to thiolates. The perfomance of pH-responsive polymer modified Gd nanoparticles was then evaluated for potential use as smart MRI CAs via monitoring the relaxivity changes upon the environmental pH changing. Furthermore, the stability of the GdNPs in pH solutions has also been studied to ensure the potential use under different environmental pH. The results suggested that the pH-responsive polymers can be used to effectively modify the Gd nanoparticles surface to prepare a smart contrast agent for MRI, which will potentially allow for enhanced diagnostics in the treatment of cancer.
Associated Publications
Rights
Copyright of the original work is retained by the author.