Polymer-Stabilized Perfluorobutane Nanodroplets for Ultrasound Imaging Agents

Abstract

In this paper, we describe a method for the stabilization of low-boiling point (low-bp) perfluorocarbons (PFCs) at physiological temperatures by an amphiphilic triblock copolymer which can emulsify PFCs and be cross-linked. After UV-induced thiol-ene cross-linking, the core of the PFC emulsion remains in liquid form even at temperatures exceeding their boiling points. Critically, the formulation permits vaporization at rarefactional pressures relevant for clinical ultrasound.

Controlling nanoemulsion surface chemistry with poly(2-oxazoline) amphiphiles

“…94 Historically, peruorocarbon (PFC) nanoemulsions have been stabilized by Pluronic F-68 (1) for use as articial blood substitutes; 95 however, these surfactants have been associated with formulation inconsistencies and multidose toxicity. [96][97][98] Contemporary applications of PFC nanoemulsions such as 19 F-magnetic resonance imaging, 51,99,100 ultrasound contrast agents, 45,101 photodynamic therapy, 92,102 and intracellular sensors 103 have spawned interest in new formulations. We previously looked to commercially available polymers and biomolecules for the stabilization and surface functionalization of PFC emulsions, but found these materials unsuitable due to large size and rapid degradation of the droplets, as well as limitations in postemulsion functionalization.…”

“…We previously looked to commercially available polymers and biomolecules for the stabilization and surface functionalization of PFC emulsions, but found these materials unsuitable due to large size and rapid degradation of the droplets, as well as limitations in postemulsion functionalization. 90 Recently, volatile per-uorocarbon droplets have been effectively stabilized by Gianneschi and coworkers through triblock poly(norbornene)s, 45 and by Medina et al through crosslinked peptides. 44 However, neither of these efforts explored surface modication.…”

“…Simple surfactants such as phospholipids and poloxamers ( Fig. 1B) are routinely used for industrial applications, while recently engineered peptide, [42][43][44] polymer, 45 and nanoparticle 46 surfactants have produced responsive materials 47,48 and sophisticated architectures. Slight changes in surfactant structure can drastically affect the physiochemical properties of the emulsions.…”

Novel method for the formation of monodisperse superheated perfluorocarbon nanodroplets as activatable ultrasound contrast agents

“…Specifically, emulsification of low boiling point PFCs into stable NDs is dificult and the products are typically of limited shelf-life, 36,37 prompting search for stabilizing techniques. 38 The most commonly used and favored method of producing low boiling point (<0 °C) nanodroplets of liquid decafluorobutane (DFB) (BP = −1.7 °C) or octafluoropropane (OFP) (BP =−36.7 °C) begins by producing MBs using sonication or high-speed mechanical agitation of the dispersion medium with the PFC vapor present in the headspace. 36,37,39–41 While this approach results in successful production of PCCAs, the resulting NDs have a wide size distribution requiring filtering of the final sample, 42 relatively low particle counts, and most importantly, a large number of ~100 nm-sized likely non PFC-filled liposomes that are generated during MB production and condensation.…”

A Yolk–Shell Nanoplatform for Gene‐Silencing‐Enhanced Photolytic Ablation of Cancer

“…Due to the PPy core and loading of PFH, the PTC‐siRNA/PFH platform is expected to possess both PA imaging and contrast‐enhanced US imaging ability. PA imaging is a promising technique, which could provide preferable spatial resolution compared with traditional optical imaging modalities, while US imaging has been widely used in clinic with relatively low cost . To verify whether the mesoporous silica shell has influences on PA imaging, PA signals of PTC‐siRNA/PFH are first detected in vitro.…”