Echogenicity enhancement by end-fluorinated polylactide perfluorohexane nanocapsules: Towards ultrasound-activable nanosystems

Autor: Camille Dejean, Rilton Alves de Freitas, Guilherme Fadel Picheth, Sophie Houvenagel, Nicolas Tsapis, Laurence Moine, Olivier Couture
Přispěvatelé: Institut Galien Paris-Sud (IGPS), Université Paris-Sud - Paris 11 (UP11)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Institut de Mathématiques de Bourgogne [Dijon] (IMB), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Bourgogne (UB)
Rok vydání: 2017
Předmět:
Zdroj: Acta Biomaterialia
Acta Biomaterialia, Elsevier, 2017, 64, pp.313-322. ⟨10.1016/j.actbio.2017.10.002⟩
ISSN: 1742-7061
DOI: 10.1016/j.actbio.2017.10.002
Popis: Polylactide (PLA) polymers containing five distinct lengths of fluorinated (from C 3 F 7 to C 13 F 27 ) and non-fluorinated (C 6 H 13 ) end-groups were successfully synthesized by ring-opening polymerization of d,l -lactide. Fluorination was expected to increase the encapsulation efficiency of perfluorohexane (PFH). 150 nm nanocapsules were obtained and 19 F nuclear magnetic resonance revealed that nanocapsules formulated with fluorinated polymers increased by 2-fold the encapsulation efficiency of PFH compared with non-fluorinated derivatives, without any effect of fluorine chain length. Fluorination of the polymers did not induce any specific in vitro cytotoxicity of nanocapsules towards HUVEC and J774.A1 cell lines. The echogenicity of fluorinated-shelled nanocapsules was increased by 3-fold to 40-fold compared to non-fluorinated nanocapsules or nanoparticles devoid of a perfluorohexane core for both conventional and contrast-specific ultrasound imaging modalities. In particular, an enhanced echogenicity and contrast-specific response was observed as the fluorinated chain-length increased, probably due to an increase of density and promotion of bubble nucleation. When submitted to focused ultrasound, both intact and exploded nanocapsules could be observed, also with end-group dependency, indicating that PFH was partly vaporized. These results pave the way to the design of theranostic perfluorohexane nanocapsules co-encapsulating a drug for precision delivery using focused ultrasound. Statement of Significance We have synthesized novel fluorinated polyesters and formulated them into nanocapsules of perfluorohexane as ultrasound contrast agents. This nanosystem has been thoroughly characterized by several techniques and we show that fluorination of the biodegradable polymer favors the encapsulation of perfluorohexane without producing further reduction of cell viability. Contrary to nanocapsules of perfluoroctyl bromide formulated with the fluorinated polymers [32], the presence of the fluorinated moieties leads to an increase of echogenicity that is dependent of the length of the fluorinated moiety. Morevover, the ability of nanocapsules to explode when submitted to focused ultrasound also depends on the length of the fluorinated chain. These results pave the way to theranostic perfluorohexane nanocapsules co-encapsulating a drug for precision delivery using focused ultrasound.
Databáze: OpenAIRE
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