Christine Pépin (Avignon) - Ultrasound-sensitive perfluorocarbon nanodroplets for theranostic applications

Besides their well-known and wide use in diagnostics, the therapeutic use of ultrasounds has recently emerged.[1] In this field, perfluorocarbon (PFC) emulsion nanoparticles are increasingly investigated as ultrasound (US) contrast agents and ultrasonically enhanced drug delivery vehicles[2]. Within this framework, our team has been working for several years on the production of stable perfluorocarbon droplets optimized for both early detectio of tumor development and controlled therapy. These "theranostic tools" consist of perfluorooctyl bromide (PFOB) droplets stabilized and dispersed in water thanks to a shell resulting from the self-assembling of tailor-made fluorinated surfactants called “FTAC” and “Dendri-TAC”. Due to the fluorophilic property of perfluorocarbons, it is not possible to encapsulate any drug, even hydrophobic, within the droplet core. To do so, we used a mixture of PFOB/biocompatible oil in different ratios to prepare our nanoemulsions (NEs)[3]. Playing on several parameters like the surfactant type, surfactant/[PFOB-oil] ratio, emulsification process we produced nanodroplets with an interesting mean diameter (Do < 100 nm) for medicinal applications. We also succeeded in limiting the nanodroplets growth by a freeze-drying step, affording dry formulations of PFOB (Figure 1) easy to store and ready to use after rehydration with almost no change in droplet size and PFOB composition.4 Once optimized, a fluorescent dye was encapsulated onto the PFC/oil nanodroplets in order to allow their in vivo monitoring and visualization of tumor accumulation after intravenous injection in mice. This presentation will cover all the NEs optimization, drug or dye encapsulation, US-triggered dye/drug release and biological validation (in vitro and in vivo studies) of these new ultrasound-sensitive theranostic tools.

Figure 1. From liquid to dry nanoemulsions of PFOB
[1] J. Escoffre, A. Bouakaz, Therapeutic Ultrasound, Advances in Experimental Medicine and Biology, 880, (2016)
[2] Y. Zhou, Journal of Therapeutic Ultrasound, 3:20 (2015)
[3] K. Astafyeva, L. Somaglino, S. Desgranges, R. Berti, C. Patinote, D. Langevin, R. Salomir, A. Polidori, C. Contino-Pépin,
W. Urbach, and N. Taulier, J. Mater. Chem. B 3, 2892-2907 (2015)
[4]. WO 2016/185425 A1, «DendriTAC and their use as theranostics » Nanoemulsion (NE)