Ion-responsive 19F MRI contrast agents for the detection of cancer cells

Zhang, Cheng, Moonshi, Shehzahdi Shebbrin, Peng, Hui, Puttick, Simon, Reid, James, Bernardi, Stefano, Bernhardt, Debra J. and Whittaker, Andrew K. (2016) Ion-responsive 19F MRI contrast agents for the detection of cancer cells. ACS Sensors, 1 6: 757-765. doi:10.1021/acssensors.6b00216

Author Zhang, Cheng
Moonshi, Shehzahdi Shebbrin
Peng, Hui
Puttick, Simon
Reid, James
Bernardi, Stefano
Bernhardt, Debra J.
Whittaker, Andrew K.
Title Ion-responsive 19F MRI contrast agents for the detection of cancer cells
Journal name ACS Sensors   Check publisher's open access policy
ISSN 2379-3694
Publication date 2016-05-05
Year available 2016
Sub-type Article (original research)
DOI 10.1021/acssensors.6b00216
Open Access Status Not yet assessed
Volume 1
Issue 6
Start page 757
End page 765
Total pages 9
Place of publication Washington, DC, United States
Publisher American Chemical Society
Language eng
Subject 1502 Bioengineering
1507 Fluid Flow and Transfer Processes
1508 Process Chemistry and Technology
3105 Instrumentation
Abstract Stimuli-responsive contrast agents (CAs) show great promise for the early detection and understanding of cancer. In particular, CAs that respond to ion content may allow monitoring of both the development of cancer and the efficacy of novel therapies. Understanding the responsive behavior of stimuli-responsive CAs in different ionic environments requires development of more advanced characterization methods. Here we report a high-resolution NMR and molecular dynamics (MD) study of conformational changes of ion-responsive F copolymers of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and 2,2,2-trifluoroethyl acrylate (TFEA) (poly(OEGMA-co-TFEA)) in the presence of salt. H 2D NOESY spectra were collected with and without the presence of NaCl and demonstrated that further separation of OEGMA and TFEA segments and closer association of OEGMA side chain were observed with the addition of NaCl. MD simulations provided additional information on the changes in conformation and were consistent with the experimental findings. Furthermore, we investigated the behavior of polymer internalized by normal and cancer cells (MCF-12A and MCF-7) by monitoring the F spin-spin relaxation time (T) of poly(OEGMA-co-TFEA) copolymer in vitro. The F NMR T value we obtained in MCF-7 cancer cells (82.3 ms) is much lower than that in MCF-12A normal cells (124.2 ms), and the difference is sufficient to obtain contrast using modern magnetic resonance imaging methods in high field scanners. Our results encourage further attempts to develop even more potent CAs. This would also result in novel methods that allow monitoring of cancer at the cellular and molecular level.
Keyword Chemistry, Multidisciplinary
Nanoscience & Nanotechnology
Science & Technology - Other Topics
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID CE140100036
Institutional Status UQ

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Created: Sun, 29 May 2016, 22:53:30 EST by Simon Puttick on behalf of Aust Institute for Bioengineering & Nanotechnology