The effect of cationic groups on the stability of ¹⁹F MRI contrast agents in nanoparticles

Abstract

Fluorine‐19 (19F)‐based contrast agents are increasingly used for magnetic resonance imaging. Conjugated to polymers, they provide an excellent quantitative imaging tool to detect the movement of the polymeric nanoparticles in vivo as there is no background signal in tissue. One of the challenges is the decline in signal intensity when the conjugated hydrophobic fluorinated functionalities aggregate. Therefore, a new fluorinated monomer was prepared from l‐arginine that carries a 2,2,2‐trifluoroethyl functional group for imaging. The resulting monomer, 2,2,2‐trifluoroethylamide l‐arginine methacrylamide (3FArgMA), was copolymerized with poly(ethylene glycol) methyl ether methacrylate (PEGMEMA), [2‐(2,3,4,6‐tetra‐O‐acetyl‐α‐d‐mannopyranosyloxy)ethyl methacrylate or 1‐O‐methacryloyl‐2,3:4,5‐di‐O‐isopropylidene‐β‐d‐fructopyranose, respectively, using poly(methyl methacrylate) macro‐reversible addition–fragmentation chain transfer polymerization agent. The resulting block copolymers, which varied in 3FArgMA content, were self‐assembled into micelles of hydrodynamic diameters from 25 to 60 nm. The permanently positively charged arginine functionality on the 3FArgMA displayed repulsive forces against aggregation enabling high spin–spin relaxation times (T2) in acidic as well as alkaline solutions. However, the longer poly(ethylene glycol) side functionality in PEGMEMA enabled better steric stabilization (T2~30 ms) while the short fructose side chain was not enough to maintain high T2 values, in particular when a higher 3FArgMA content was used. © 2019 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2019, 57, 1994–2001

Investigation of segmental reorganization within amphiphilic block polymer nanoparticles derived from shell crosslinked micelle templates: Shell crosslinked knedel‐like inversion

“…Measurements 1 H NMR spectra of solutions were recorded at 300 MHz on a Varian Gemini 300 spectrometer with the solvent proton resonance used as reference. 13 C NMR spectra were recorded at 75.4 MHz as solutions on a Varian Gemini 300 spectrometer with the solvent carbon signal as reference.…”

“…In the 1990's, supramolecular assembly of amphiphilic block polymers in selective solvents, which thermodynamically favor one of the blocks, emerged as a general technique for the generation of micellar structures having morphological diversity. [1][2][3][4][5][6][7] Over the past couple of decades, tuning the composition and architecture of the block polymer building blocks [8][9][10][11][12][13][14][15][16] and incorporating environmentally responsive chemical functionalities have been shown to promote morphological switching and lead to enhanced behaviors and functions. [17][18][19][20][21][22][23][24] The covalent stabilization of micelles and other supramolecular assemblies was also recognized as a powerful method, analogous to that utilized in biology, 25 for the rapid and large-scale preparation of intricate and stable nanostructured materials.…”

Tailor-made glycopolymersviareversible deactivation radical polymerization: design, properties and applications

“…Recently, glycomonomers have been copolymerized with fluorine (F) containing monomers to achieve stable and targetable 19 F MRI contrast agents. 229,230 The Whittaker group synthesized a redox-responsive branched fluorinated glycopolymer based on 2-((1,1,1,3,3,3-hexafluoropropan-2-yl)oxy)ethyl acrylate (HFEA) and a d -glucose glycomonomer (GlcA) in the presence of a disulfide containing crosslinker. Under the reductive environment of cancer cells, the polymer undergoes a branched to linear topological transformation which leads to a substantial increase of the MRI signal (Scheme 16).…”

New Light in Polymer Science: Photoinduced Reversible Addition-Fragmentation Chain Transfer Polymerization (PET-RAFT) as Innovative Strategy for the Synthesis of Advanced Materials

“…At the completion of the RAFT polymerization most of the chains are still living, which means that at the ω-end there is the thiocarbonylthio group. This end-capped homopolymer can be seen as a macro RAFT agent and can be used to re-initiate the polymerization with a second different monomer, thereby achieving complex architectures such as block copolymers [ 10 ], star, branched, surface grafting or nanoparticles [ 11 , 12 , 13 , 14 ].…”