The internal structure of gadolinium and perfluorocarbon-loaded polymer nanoparticles affects 19F MRI relaxation times

Abstract

¹⁹F magnetic resonance imaging (¹⁹F MRI) is an emerging technique for quantitative imaging in novel therapies, such as cellular therapies and theranostic nanocarriers. Nanocarriers loaded with liquid perfluorocarbon (PFC) typically have a (single) core–shell structure with PFC in the core due to the poor miscibility of PFC with organic and inorganic solvents. Paramagnetic relaxation enhancement acts only at a distance of a few angstroms. Thus, efficient modulation of the ¹⁹F signal is possible only with fluorophilic PFC-soluble chelates. However, these chelates cannot interact with the surrounding environment and they might result in image artifacts. Conversely, chelates bound to the nanoparticle shell typically have a minimal effect on the ¹⁹F signal and a strong impact on the aqueous environment. We show that the confinement of PFC in biodegradable polymeric nanoparticles (NPs) with a multicore structure enables the modulation of longitudinal (T₁) and transverse (T₂) ¹⁹F relaxation, as well as proton (¹H) signals, using non-fluorophilic paramagnetic chelates. We compared multicore NPs versus a conventional single core structure, where the PFC is encapsulated in the core(s) and the chelate in the surrounding polymeric matrix. This modulated relaxation also makes multicore NPs sensitive to various acidic pH environments, while preserving their stability. This effect was not observed with single core nanocapsules (NCs). Importantly, paramagnetic chelates affected both T₁ and T₂¹⁹F relaxation in multicore NPs, but not in single core NCs. Both relaxation times of the ¹⁹F nucleus were enhanced with an increasing concentration of the paramagnetic chelate. Moreover, as the polymeric matrix remained water permeable, proton enhancement additionally was observed in MRI.