Phase change contrast agents for
ultrasound (US) imaging consist of nanodroplets (NDs) with a perfluorocarbon
(PFC) liquid core stabilized with a lipid or a polymer shell. Liquid
↔ gas transition, occurring in the core, can be triggered by
US to produce acoustically active microbubbles (MBs) in a process
named acoustic droplet vaporization (ADV). MB shells containing polymerized
diacetylene moiety were considered as a good trade off between the
lipid MBs, showing optimal attenuation, and the polymeric ones, displaying
enhanced stability. This work reports on novel perfluoropentane and
perfluorobutane NDs stabilized with a monolayer of an amphiphilic
fatty acid, i.e. 10,12-pentacosadiynoic acid (PCDA), cured with ultraviolet
(UV) irradiation. The photopolymerization of the diacetylene groups,
evidenced by the appearance of a blue color due to the conjugation
of ene-yne sequences, exhibits a chromatic transition from the nonfluorescent
blue color to a fluorescent red color when the NDs are heated or the
pH of the suspension is basic. An estimate of the molecular weights
reached by the polymerized PCDA in the shell, poly(PCDA), has been
obtained using gel permeation chromatography and MALDI-TOF mass spectrometry.
The poly(PCDA)/PFC NDs show good biocompatibility with fibroblast
cells. ADV efficiency and acoustic properties before and after the
transition were tested using a 1 MHz probe, revealing a resonance
frequency between 1 and 2 MHz similar to other lipidic MBs. The surface
of PCDA shelled NDs can be easily modified without influencing the
stability and the acoustic performances of droplets. As a proof of
concept we report on the conjugation of cyclic RGD and PEG chains
of the particles to support targeting ability toward endothelial cells.