Perfluorocarbon nanodroplets stabilized by fluorinated surfactants: characterization and potentiality as theranostic agents

Abstract

We aim to produce emulsions that can act as contrast agents and drug carriers for cancer imaging and therapy. To increase tumor detection and decrease drug side effects, it is desirable to take advantage of the enhanced permeability and retention effect that allows nanoparticles to accumulate in tumor tissues.To do so, the emulsion droplets need to be small enough and stable over time in addition to enhancing image contrast and carrying a drug payload. In the present study, we have investigated the properties and potentiality as theranostic agents of perfluorocarbon emulsions stabilized by a biocompatible fluorinated surfactant called FTAC. To obtain better control of our system, the synthesis of those surfactants was studied and their physico-chemical properties were explored in different configurations such as micelles, in the perfluorocarbon droplet shell and at water/air and water/perfluorocarbon interfaces. The originality of this work lies in the determination of numerous characteristics of emulsions and fluorinated surfactants including surface tension, interfacial tension, critical micelle concentration, adiabatic compressibility, density, size distribution (aging studies), and ultrasonic echogenicity. These characterization studies were conducted using different types of FTAC and several perfluorocarbons (perfluoropentane, perfluorohexane, and perfluorooctyl bromide). We have also shown that a hydrophobic drug could be encapsulated in the FTAC-stabilized perfluorocarbon droplets thanks to triacetin addition. Finally, the perfluorocarbon emulsions were detectable in vitro by a clinical 3 T MRI scanner, equipped with a double frequency 19 F/ 1 H transmit-receive coil.

Micron-sized PFOB liquid core droplets stabilized with tailored-made perfluorinated surfactants as a new class of endovascular sono-sensitizers for focused ultrasound thermotherapy

“…40 PFC droplets need to be stabilised with amphiphilic molecules such as lipids or fluorinated surfactants. 41 The present study uses in-house surfactants called F-TAC which consist of a fluorinated hydrophobic moiety exhibiting a high affinity for PFC droplets and a hydrophilic moiety made of a polyTRIS oligomer 42 (See Figure 1a). Contrary to commercially available fluorinated surfactants often used in the literature, such as ZONYL (Dupont De Nemours) and CAPSTONE (Chemours), F-TAC surfactants exhibit a good biocompatibility (no hemolytic activity, LD 50 up to 4.5g/kg in rats after i.v.…”

Hollow Nanospheres with Fluorous Interiors for Transport of Molecular Oxygen in Water

“…A wide range of compatibilizing agents/systems have been proposed for suspending SFCs in water, including lipids, block copolymers, and proteins. The oleophobicity of fluorous compounds tends to destabilize SFC emulsions, thus rendering common dispersion approaches only a temporary success. Incorporation of SFC liquids into self‐assembled polymer nanocapsules led to stable and useful formulations .…”

Impact of Polylactide Fluorinated End-Group Lengths and Their Dynamics on Perfluorohexane Microcapsule Morphology

“…Nonetheless, the entrapment of fully fluorinated PFCs, such as PFH, within a polymeric shell is proving to be difficult due to their dual lipophobic and hydrophobic character and their trend to easily evaporate during formulation 14 . Several groups have turned to the use of fluorinated surfactants or lipids to improve PFCs encapsulation [15][16][17] . Literature also reports the functionalization of polymer with fluorinated end-groups to favor interactions with PFCs 11,14,[18][19][20][21][22][23][24] .…”