Tuning the Interfacial Properties of Fluorous Colloids Toward Ultrasound Programmable Bioactivity

Abstract

Liquid-in-liquid emulsions are kinetically stable colloids that undergo liquid-to-gas phase transitions in response to thermal or acoustic stimuli. Perfluorocarbons (PFCs) are preferred species as their highly fluorinated nature imparts unique properties that are unparalleled by nonfluorinated counterparts. However, traditional methods to prepare PFC emulsions lack the ability to precisely tune the thermodynamic stability of the fluorous−water interphase and consequently control their vaporization behavior. Here, we report a privileged fluoroalkanoic acid that undergoes concentration-dependent assembly on the surfaces of fluorous droplets to modulate interfacial tension. This allows for the rational formulation of orthogonal PFC droplets that can be programmed to vaporize at specified ultrasound powers. We exploit this behavior in two exemplary biomedical settings by developing emulsions that aid ultrasound-mediated hemostasis and enable bioorthogonal delivery of molecular sensors to mammalian cells. Mechanistic insights gained from these studies can be generalized to tune the thermodynamic interfacial equilibria of PFC emulsions toward designing controllable tools for precision medicine.

Ultrasound‐Responsive Nanopeptisomes Enable Synchronous Spatial Imaging and Inhibition of Clot Growth in Deep Vein Thrombosis

“…[ 23 ] This assertion is based on our prior observations that assembly of fluorinated small molecules at the surfaces of PFC liquids alters the surface tension, decoupled from droplet size, to precisely control the US vaporization of uniform dimension emulsions. [ 24 ]…”

“…Insights explaining this behavior can be gleaned from our prior work with small molecule perfluoroalkyl emulsifiers. [ 24 ] Here, an optimal fluoroalkyl tail length for perfluorocarboxy amphiphiles was identified that favored their preferential assembly at fluorous–water interfaces, rather than solubilization by either bulk solvent. Relating this to the current study suggests that the RGD‐3F F peptide possesses a unique counterbalance of polarity and fluorine content that is ideally suited for assembly at PFC–water interfaces.…”

“…Interfacial tension measurements at the liquid–liquid interface were performed using a ramé‐hart Model 295 automated goniometer/tensiometer, as previously described. [ 24 ] RGD‐ x F F ( x = 1–4) were individually prepared at concentrations 0, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, and 1.00 mg mL −1 solutions in 10% DMF in water. DROPimage Advanced software was used to capture pendant drop images and to analyze each droplet for interfacial tension measurements based on the Young equation.…”

Life at the interface: Engineering bio‐nanomaterials through interfacial molecular self‐assembly

“…Work from our lab has shown that non‐canonical amino acids can be directed to assemble at fluorous‐water interfaces to develop mechanically responsive thin films and viscoelastic synthetic mucus (Miller & Medina, 2024; Sloand, Culp, et al, 2021; Sloand, Rokni, et al, 2021). Mechanistic insights gained from this work enabled the development of fluorine‐rich small molecules and peptides that act as emulsifiers to stabilize perfluorocarbon nanodroplets (Kim et al, 2023; Lawanprasert et al, 2021; Medina et al, 2017; Sloand et al, 2020; Sloand, Culp, et al, 2021; Sloand, Rokni, et al, 2021). By controlling the physicochemical properties of the emulsifier, we have shown that the thermodynamic stability of phase separated emulsions can be rationally tailored to enable thermally and mechanically responsive nanomaterials.…”

Improved hybrid-shelled perfluorocarbon microdroplets as ultrasound- and laser-activated phase-change platform

“…The stabilising shell is directly involved in the bonding with the carried agents (e.g., drugs or functional nanoparticles) and in the targeting towards specific tissues [16,17], it could affect the vaporisation efficiency, and it determines the acoustic response of the MBs formed after vaporisation [18][19][20][21]. On top of these, the primary role of the shell lies in ensuring the stability and the size uniformity of MDs over time.…”