Ultrastable shelled PFC nanobubbles: A platform for ultrasound-assisted diagnostics, and therapy.

Nanoscale echogenic bubbles (NBs), can be used as a theranostic platform for the localized delivery of encapsulated drugs. However, the generation of NBs is challenging, because they have lifetimes as short as milliseconds in solution. The aim of this work has been the optimization of a preparation method for the generation of stable NBs, characterized by measuring: a) acoustic efficiency, b) nano-size, to ensure passive tumour targeting, c) stability during storage and after injection and d) ability to entrap drugs. NBs are monodisperse and ultra-stable, their stability achieved by generation of an amphiphilic multilamellar shell able to efficiently retain the PFC gas. The NBs perform as good acoustic enhancers over a wide frequency range and out of resonant conditions, as tested in both in vitro and in vivo experiments, proving to be a potential platform for the production of versatile carriers to be used in ultrasound-assisted diagnostic, therapeutic and theranostic applications. Ultra-stable NBs generation has been achieved by the optimization of a novel preparation method. These systems have been deeply characterized to assess NBs existence, in terms of physical chemical and acoustic features. The selected NBs had been tested in both in vitro and in vivo experiments, checking their capability as a potential platform for the production of versatile carriers to be used in ultrasound-assisted diagnostic, therapeutic, and theranostic applications. [Display omitted] • Generation of stable gas-filled nanobubbles • Nanobubbles are long-lived thanks to their multi-layered lipid/surfactant shell. • Nanobubbles can carry lipophilic and hydrophilic drugs. • Nanobubbles perform as good acoustic enhancers in vitro. • Nanobubbles are useful contrast agents in in vivo pilot test in a mouse model. [ABSTRACT FROM AUTHOR]