Fluorocarbon Gas Exposure Induces Disaggregation of Nanodiamond Clusters and Enhanced Adsorption, Enabling Medical Microbubble Formation

Abstract

Introducing fluorocarbon vapor in the air above an aqueous dispersion of clusters of nanodiamonds induces their disaggregation, a prerequisite for most of their biomedical uses. Furthermore, the fluorocarbon gas promotes the adsorption of nanodiamonds at the gas/water interface. As an example of the benefits that can be gained from our findings relative to the implementation of nanomaterials for practical uses, we investigated the role that a fluorocarbon gas may play in the generation of microbubbles, which are currently actively investigated in ultrasound-mediated diagnosis and therapy. Remarkably, the fluorocarbon gas enables the production of microbubbles shelled only with nanodiamonds, in the absence of any other surfactant, which could not be achieved without the fluorocarbon being present. This demonstrates that a supernatant gas can decisively affect the adsorption of nanoparticles from an aqueous phase to an air/water interface, likely through physical adsorption at the nanodiamond surface. The investigations involved solid-state NMR and FTIR, microbubble generation experiments with acoustic attenuation monitoring, and bubble profile analysis tensiometry on spontaneously adsorbed Gibbs films. Perspectives include control of aggregation of nanodiamonds and their retrieval from aqueous dispersions, and applications in multimodal diagnostic imaging, bioimaging and therapeutic cell tracking. It is proposed that the disaggregating potency of fluorocarbons can be applied to other nanomaterials, providing a simple and effective means of alleviating aggregation.

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

“…DPPC (50 mmol L −1 ) and DPPE-PEG2000 (DPPC/DPPE-PEG2000 molar ratio 9:1) were dispersed in a HEPES buffer solution (0.9 mL) by magnetic stirring for 3–6 h at 50 °C. Fifty µL of the lipopeptide solution in DMSO were injected into the phospholipid dispersion and subjected to agitation/amalgamation using a Vialmix ® device (2 cycles of 45 s, Lantheus Medical Imaging N. Billerica, MA) at room temperature and under F -hexane-saturated N 2 at room temperature (for details, see [ 39 ]). The resulting foam was immediately diluted with 5 mL of HEPES buffer.…”

“…In addition, FCs were also found to act as co-surfactants to the phospholipid molecules of the MB shell and strongly reduce its interfacial tension [ 35 – 36 ]. Recent studies have reported that the fluorine–fluorine interactions that develop between the FC and the MB shell component (e.g., fluorinated biomarkers [ 37 ] and fluorinated nanoparticles, including dendronized iron oxide nanoparticles [ 38 ] and nanodiamonds [ 39 ]) efficiently reinforce the interfacial film cohesion, thus enhancing the stability of the MBs. Various types of perfluoroalkylated amphiphiles have been reported that were designed for biomedical applications and display highly effective nanoemulsion and MB stabilizing characteristics [ 40 – 42 ].…”

Microbubbles Stabilized by Protein Shell: From Pioneering Ultrasound Contrast Agents to Advanced Theranostic Systems

“…MB formation is enabled by lowering the surface tension of solutions at the gas-liquid interface with the introduction of surfactants [18,[62][63][64]. Hence, various surfactants are used as the basis for MB fabrication.…”

Nanodiamond-Based Fibrous Composites: A Review of Fabrication Methods, Properties, and Applications

“…On the other hand, new ideas have been provided for stabilization of ND within a matrix such as ND combination with boron nitride nanosheets for a poly(vinyl alcohol) (PVA) composite film, 61 in situ synthesis of titanium carbide nanoparticles inside an Al matrix directly during mechanical alloying of Al, Ti, and ND, 59 and the introduction of fluorocarbon vapor in the air above an aqueous dispersion. 62 This topic is still under continuous progress, and it is expected that in the near future ND agglomeration will no longer be an issue.…”