Abstract

The aim of our study was to develop a novel method for nanocarriers’ preparation as a fluorine magnetic resonance imaging (19F MRI)-detectable drug delivery system. The novelty of the proposed approach is based on the application of fluorinated polyelectrolyte Nafion as a contrast agent since typical MRI contrast agents are based on paramagnetic gadolinium or ferro/superparamagnetic iron oxide compounds. An advantage of using an 19F-based tracer comes from the fact that the 19F image is detected at a different resonance frequency than the 1H image. In addition, the close to zero natural concentration of 19F nuclei in the human body makes fluorine atoms a promising MRI marker without any natural background signal. That creates the opportunity to localize and identify only exogenous fluorinated compounds with 100% specificity. The nanocarriers were formed by the deposition of polyelectrolytes on nanoemulsion droplets via the layer-by-layer technique with the saturation approach. The polyelectrolyte multilayer shell was composed of Nafion, the fluorinated ionic polymer used for labeling by 19F nuclei, and poly-l-lysine (PLL). The surface of such prepared nanocarriers was further pegylated by adsorption of pegylated polyanion, poly-l-glutamic acid (PGA). The 19F MRI-detectable hydrophobic nanocarriers with an average size of 170 nm and a sufficient signal-to-noise ratio have been developed and optimized to be used for passive tumor targeting and drug delivery.

Highlights

  • Nafion, developed by the DuPont in the late 1960s, is a sulfonated tetrafluoroethylene-based fluoropolymer-copolymer produced by copolymerization of a perfluorinated vinyl ether comonomer with tetrafluoroethylene, resulting in the Teflonlike backbone bearing hydrophilic sulfonic acid groups.[1]

  • It has been applied as the material for biosensors, for controlled drug release, and for the formation of antimicrobial coatings.[8−11] Since Nafion possesses 19F nuclei, it can be used for fluorine magnetic resonance imaging (19F MRI)

  • Typical MRI contrast agents are based on paramagnetic gadolinium or ferro/superparamagnetic iron oxide compounds, producing positive or negative contrast in the 1H MR image[12−14] due to the change of relaxation times T1 or T2 (T2*) caused by local disturbances of the magnetic field experienced by water molecules in the imaged object in the surrounding of the contrast agent

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Summary

Introduction

Nafion, developed by the DuPont in the late 1960s, is a sulfonated tetrafluoroethylene-based fluoropolymer-copolymer produced by copolymerization of a perfluorinated vinyl ether comonomer with tetrafluoroethylene, resulting in the Teflonlike backbone bearing hydrophilic sulfonic acid groups.[1] Nafion was the first synthetic polymer ever developed with ionic properties, and it started an entirely new class of polymers called ionomers.[2] It combines the physical and chemical properties of its Teflon base material with ionic characteristics, which results in specific properties: resistance to chemicals, relatively high working temperatures compared to other polymers, high ion conductivity (a cation exchange polymer), and very selective and high permeability for water.

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