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

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 behaviour 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 19 F co-polymers of oligo(ethylene glycol) methyl ether methacrylate (OEGMA) and 2,2,2-trifluoroethyl acrylate (TFEA) (poly(OEGMA-co-TFEA)) in the presence of salt. 1 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 behaviour of polymer internalised by normal and cancer cells (MCF-12A and MCF-7) by monitoring the 19 F spin-spin relaxation time (T2) of poly(OEGMA-co-TFEA) copolymer in vitro. The 19 F NMR T2 values 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 MRI 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.

Low‐cost LED‐based Photo‐CIDNP Enables Biocompatible Hyperpolarization of 19F for NMR and MRI at 7 T and 4.7 T

“…Fluorinated substrates are well established drugs and diagnostic pharmaceuticals in many medical applications, such as the antidepressant fluoxetine or the inhalational anesthetic desflurane ,. Even their potential as contrast agents has already been demonstrated . Due to the importance of these substrates in medicine, studies on the pharmacokinetics, metabolism, interaction with other biomolecules, or localization of the site of pharmacological action increasingly use MRS and MRI techniques because these enable non‐invasive three‐dimensional and time‐resolved detection of structures and dynamics of NMR‐detectable substrates, proteins, and biological tissue.…”

Atomistic insights on the LCST behavior of PMEO2MA in water by molecular dynamics simulations

“…Hao et al investigated the LCST behavior of copolymers between polycaprolactone and OEGMAs and their interactions with doxorubicin (DOX) by both experimental and coarse‐grained MD methods . Zhang et al reported the conformational changes of the copolymers between OEGMA and 2,2,2‐trifluoroethyl acrylate [poly(OEGMA‐ co ‐TFEA)] during the phase transition by means of NMR and MD techniques . To the best of our knowledge, there is not any study only on OEGMA‐based homopolymers yet that was carried out by MD simulations.…”

Antimicrobial anilinium polymers: The properties of poly(N,N‐dimethylaminophenylene methacrylamide) in solution and as coatings

“…The cytotoxicity of MeI‐PDMAPMA was evaluated using 3T3 fibroblast cells through a 3‐(4,5‐dimethylthiazol‐2‐yl)‐5‐(3‐carboxymethoxyphenyl)‐2‐(4‐sulfophenyl)‐2H‐tetrazolium inner salt (MTS) assay. The procedure was based on a protocol previously reported . Briefly, 3T3 fibroblast cells were cultured in DMEM with 10% fetal bovine serum and 1% antibiotic–antimycotic, incubated at 37 °C for 24 h with 5% CO 2 .…”