Self-Assembled Thermoresponsive Polymeric Nanogels for ¹⁹F MR Imaging

Abstract

Magnetic resonance imaging using fluorinated contrast agents (F MRI) enables to achive highcontrast in images due to the negligible fluorine background in living tissues. In this pilot study, we developed new biocompatible, temperature-responsive, and easily synthesized polymeric nanogels containing a sufficient concentration of magnetically equivalent fluorine atoms for F MRI purposes. The structure of the nanogels is based on amphiphilic copolymers containing two blocks, a hydrophilic poly[ N-(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) block, and a thermoresponsive poly[ N(2,2difluoroethyl)acrylamide] (PDFEA) block. The thermoresponsive properties of the PDFEA block allow us to control the process of nanogel self-assembly upon its heating in an aqueous solution. Particle size depends on the copolymer composition, and the most promising copolymers with longer thermoresponsive blocks form nanogels of suitable size for angiogenesis imaging or the labeling of cells (approximately 120 nm). The in vitroF MRI experiments reveal good sensitivity of the copolymer contrast agents, while the nanogels were proven to be noncytotoxic for several cell lines.

SET‐LRP Synthesis of Well‐Defined Light‐Responsible Block Copolymer Micelles

“…The formation of micelles for PEG‐based block copolymers is widely reported in the literature, and therefore, our assumption is very realistic. The cmc of the block copolymer was measured in PBS by fluorescence spectroscopy in the presence of pyrene (Figure S1, Supporting Information) and the obtained value (cmc = 8.1 mg L −1 ) was similar to the values previously reported for other block copolymers …”

Fluorine polymer probes for magnetic resonance imaging: quo vadis?

“…Various types of fluorinated agents are available in the form of fluorinated perfluorocarbon (PFC) nanoemulsions [37], fluorinated lanthanide chelates [2, 6], fluorinated nucleotides [32], fluoride-based nanocrystals [38], multicompartment amphiphilic polymers [19, 39–41], etc. A brief overview of fluorine-containing probes, including their systematic names, abbreviations, chemical structures, molecular weights and fluorine content, can be found in Table 1.…”

“…These probes can carry large amounts of fluorine atoms, resulting in a high sensitivity of visualization, although their short relaxation times resulting from polymerization need to be adjusted. In the majority of these amphiphilic agents, the fluorinated block is based on acrylic acid, specifically on 2,2,2-trifluorethylacrylate (TFEA), 2,2,2-trifluorethyl methacrylate (TFEMA), poly[ N -(2,2-difluorethyl)acrylamide] (PDFEA) [39, 40] or octafluoropentyl methacrylate (OFPMA). There are also polymers based on functionalized styrenes (e.g., 2,3,4,5,6-pentafluorostyrene (PFS)) [51] or polydimethylsiloxanes (PDMS) [52].…”

“…Self-assembled biocompatible polymer nanogels consisting of hydrophilic-thermoresponsive diblock copolymers containing either poly[ N -(2-hydroxypropyl)methacrylamide] (PHPMA) or poly(2-methyl-2-oxazoline) (PMeOx) as the hydrophilic block and PDFEA as the fluorinated thermoresponsive block exhibited thermal responsivity, being molecularly soluble at room temperature and forming well-defined nanogels at body temperature (Fig. 1) [39]. The probes exhibit suitable relaxation times ( T 1 ≈ 275–312 ms, T 2 ≈ 17–305 ms; at 4.7 T, 37 °C) for visualization by 19 F MRI using standard spin-echo sequences.…”

“…6.5 nm) at temperatures below 23 °C and undergoes self-assembly into nanogel particles (hydrodynamic radius R h approx. 77 nm at 37 °C) above this temperature [39]

Fig. 2A scheme of self-assembling nanoparticles containing a hydrophilic shell and a fluorine-containing core ( a ).

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