Ion-Responsive 19F MRI Contrast Agents for the Detection of Cancer Cells

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• 作者：Cheng Zhang ; Shehzahdi Shebbrin Moonshi ; Hui Peng ; Simon Puttick ; James Reid ; Stefano Bernardi ; Debra J. Searles ; Andrew K. Whittaker
• 刊名：ACS Sensor
• 出版年：2016
• 出版时间：June 24, 2016
• 年：2016
• 卷：1
• 期：6
• 页码：757-765
• 全文大小：702K
• ISSN：2379-3694

文摘

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 ¹⁹F 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. ¹H 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 ¹⁹F spin–spin relaxation time (Tb>2b>) of poly(OEGMA-co-TFEA) copolymer in vitro. The ¹⁹F NMR Tb>2b> 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.