Cell Labeling for 19F MRI: New and Improved Approach to Perfluorocarbon Nanoemulsion Design

Abstract

This report describes novel perfluorocarbon (PFC) nanoemulsions designed to improve ex vivo cell labeling for 19F magnetic resonance imaging (MRI). 19F MRI is a powerful non-invasive technique for monitoring cells of the immune system in vivo, where cells are labeled ex vivo with PFC nanoemulsions in cell culture. The quality of 19F MRI is directly affected by the quality of ex vivo PFC cell labeling. When co-cultured with cells for longer periods of time, nanoemulsions tend to settle due to high specific weight of PFC oils (1.5–2.0 g/mL). This in turn can decrease efficacy of excess nanoemulsion removal and reliability of the cell labeling in vitro. To solve this problem, novel PFC nanoemulsions are reported which demonstrate lack of sedimentation and high stability under cell labeling conditions. They are monodisperse, have small droplet size (~130 nm) and low polydispersity (<0.15), show a single peak in the 19F nuclear magnetic resonance spectrum at −71.4 ppm and possess high fluorine content. The droplet size and polydispersity remained unchanged after 160 days of follow up at three temperatures (4, 25 and 37 °C). Further, stressors such as elevated temperature in the presence of cells, and centrifugation, did not affect the nanoemulsion droplet size and polydispersity. Detailed synthetic methodology and in vitro testing for these new PFC nanoemulsions is presented.

Design and formulation of nanoemulsions using 2-(poly(hexafluoropropylene oxide)) perfluoropropyl benzene in combination with linear perfluoro(polyethylene glycol dimethyl ether)

“…To explore FLD utility more fully, we investigated two different hydrocarbon oils separately and a combination of those two. One was olive oil (super refined), which has been previously used in other formulations in our lab and has been found to contribute to colloidal stability of PFC nanoemulsions [44]. The other oil investigated was Capmul® PG-8 NF (Propylene Glycol Monocaprylate) which is known as a good solubilizer for highly water insoluble drugs.…”

Dual Nanoparticle Conjugates for Highly Sensitive and Versatile Sensing Using 19F Magnetic Resonance Imaging

“…19 F MR images can be overlayed with anatomical 1 H MR images to give complementary information. [8][9][10] There has been interest in fluorine-containing nanoparticles for 19 F MRI, as they encapsulate a large concentration of highly fluorinated molecules in aqueous media, using either phospholipids, [11] polymeric surfactants, [12][13][14] or solid coatings such as silica. [15] Phospholipid coated perfluorocarbon nanoemulsions have been used for cell labelling ex vivo [16][17][18][19][20][21] and uptake in vivo to track macrophages.…”

19F MRI-fluorescence imaging dual-modal cell tracking with partially fluorinated nanoemulsions

“…Notably, the extremely low solubility and interaction of fluorescent dyes in PFCs may cause aggregation-induced quenching (ACQ) of fluorescence, difficulties in encapsulation, and early release of fluorescent dyes ( Würthner et al, 2011 ; Battistelli et al, 2016 ). Moreover, the high density of PFCs and their nanoemulsions may cause low cell uptake, cell damage, and misleading results ( Patel et al, 2013 ). To address these issues, we recently used partially fluorinated agents, hydrofluorocarbons (HFCs), as alternatives for PFCs ( Chen et al, 2022 ; Wu et al, 2022 ).…”