Nanoparticles for “two color” 19F magnetic resonance imaging: Towards combined imaging of biodistribution and degradation

Olga Koshkina,Paul B White,Alexander H.J Staal,Ralf Schweins,Edyta Swider,Ilaria Tirotta,Paul Tinnemans,Remco Fokkink,Andor Veltien,N Koen Van Riessen,Ernst R.H Van Eck,Arend Heerschap,Pierangelo Metrangolo,Francesca Baldelli Bombelli,Mangala Srinivas

doi:10.1016/j.jcis.2019.12.083

Abstract

The use of polymeric nanoparticles (NPs) as therapeutics has been steadily increasing over past decades. In vivo imaging of NPs is necessary to advance the therapeutic performance. 19F Magnetic Resonance Imaging (19F MRI) offers multiple advantages for in vivo imaging. However, design of a probe for both biodistribution and degradation has not been realized yet. We developed polymeric NPs loaded with two fluorocarbons as promising imaging tools to monitor NP biodistribution and degradation by 19F MRI.These 200 nm NPs consist of poly(lactic-co-glycolic acid) (PLGA) loaded with perfluoro-15-crown-5 ether (PFCE) and PERFECTA. PERFECTA/PFCE-PLGA NPs have a fractal sphere structure, in which both fluorocarbons are distributed in the polymeric matrix of the fractal building blocks, which differs from PFCE-PLGA NPs and is unique for fluorocarbon-loaded colloids. This structure leads to changes of magnetic resonance properties of both fluorocarbons after hydrolysis of NPs.PERFECTA/PFCE-PLGA NPs are colloidally stable in serum and biocompatible. Both fluorocarbons show a single resonance in 19F MRI that can be imaged separately using different excitation pulses. In the future, these findings may be used for biodistribution and degradation studies of NPs by 19F MRI in vivo using “two color” labeling leading to improvement of drug delivery agents.

Highlights

Polymeric nanotherapeutics have been developed for several decades, as they promise to improve the delivery of drugs and reduce side effects, and can have a strong impact on a treatment of various diseases [1,2,3]
The solution of poly(lactic-co-glycolic acid) (PLGA), PERFECTA, and perfluoro-15crown-5 ether (PFCE) in HFIP was added to aqueous solution of poly(vinyl alcohol) (PVA) as a nonionic surfactant and emulsified using sonication to provide the energy that is required for encapsulation of fluorocarbons [28]
Our goal was to show that the encapsulation of two fluorocarbons within the same particle could be used for imaging of biodistribution and degradation of polymeric drug carriers

Summary

Introduction

Polymeric nanotherapeutics have been developed for several decades, as they promise to improve the delivery of drugs and reduce side effects, and can have a strong impact on a treatment of various diseases [1,2,3]. The 19F nucleus has a unique combination of characteristics for imaging: (1) it has no endogenous background signal [10], (2) it displays a broad chemical shift for simultaneous “multi-color” in vivo tracking of different compounds [11,12,13,14], and, (3) the obtained signal is linearly correlated to the amount of fluorine atoms, enabling quantitative imaging [15] These properties make 19F MRI suitable for in vivo tracking of the biodistribution of labeled cell therapies [15,16,17,18,19], drug carriers [20,21], and molecular imaging agents [22]. None of the other imaging modalities combine all of these features

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