title: Functionalized multiwalled carbon nanotubes as ultrasound contrast agents.
abstract: Ultrasonography is a fundamental diagnostic imaging tool in everyday clinical practice. Here, we are unique in describing the use of functionalized multiwalled carbon nanotubes (MWCNTs) as hyperechogenic material, suggesting their potential application as ultrasound contrast agents. Initially, we carried out a thorough investigation to assess the echogenic property of the nanotubes in vitro. We demonstrated their long-lasting ultrasound contrast properties. We also showed that ultrasound signal of functionalized MWCNTs is higher than graphene oxide, pristine MWCNTs, and functionalized single-walled CNTs. Qualitatively, the ultrasound signal of CNTs was equal to that of sulfur hexafluoride (SonoVue), a commercially available contrast agent. Then, we found that MWCNTs were highly echogenic in liver and heart through ex vivo experiments using pig as an animal model. In contrast to the majority of ultrasound contrast agents, we observed in a phantom bladder that the tubes can be visualized within a wide variety of frequencies (i.e., 5.5-10 MHz) and 12.5 MHz using tissue harmonic imaging modality. Finally, we demonstrated in vivo in the pig bladder that MWCNTs can be observed at low frequencies, which are appropriate for abdominal organs. Importantly, we did not report any toxicity of CNTs after 7 d from the injection by animal autopsy, organ histology and immunostaining, blood count, and chemical profile. Our results reveal the enormous potential of CNTs as ultrasound contrast agents, giving support for their future applications as theranostic nanoparticles, combining diagnostic and therapeutic modalities.
authors.affiliation: Dipartimento di Chimica e Farmacia, Sperimentale e Oncologica, Università degli Studi di Sassari, 07100 Sassari, Italy. lgdelogu@uniss.it
authors.forename: Lucia Gemma
authors.initials: LG
authors.lastname: Delogu
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Vidili
authors.forename: Enrica
authors.initials: E
authors.lastname: Venturelli
authors.forename: Cécilia
authors.initials: C
authors.lastname: Ménard-Moyon
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Zoroddu
authors.forename: Giovannantonio
authors.initials: G
authors.lastname: Pilo
authors.forename: Paola
authors.initials: P
authors.lastname: Nicolussi
authors.forename: Ciriaco
authors.initials: C
authors.lastname: Ligios
authors.forename: Davide
authors.initials: D
authors.lastname: Bedognetti
authors.forename: Francesco
authors.initials: F
authors.lastname: Sgarrella
authors.forename: Roberto
authors.initials: R
authors.lastname: Manetti
authors.forename: Alberto
authors.initials: A
authors.lastname: Bianco
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000032:analysis; D015214:Antigens, Differentiation, Myelomonocytic / Q000032:analysis; D017252:CD3 Complex / Q000032:analysis; D051925:CD79 Antigens / Q000032:analysis; D003287:Contrast Media / Q000737:chemistry*; D005260:Female; D007150:Immunohistochemistry; D007668:Kidney / Q000000981:diagnostic imaging / Q000378:metabolism; D008099:Liver / Q000000981:diagnostic imaging / Q000378:metabolism; D046529:Microscopy, Electron, Transmission; D036103:Nanotechnology / Q000295:instrumentation / Q000379:methods*; D037742:Nanotubes, Carbon / Q000737:chemistry* / Q000648:ultrastructure; D011956:Receptors, Cell Surface / Q000032:analysis; D015203:Reproducibility of Results; D013459:Sulfur Hexafluoride / Q000737:chemistry; D034421:Sus scrofa; D014463:Ultrasonography / Q000295:instrumentation / Q000379:methods*; D001743:Urinary Bladder / Q000000981:diagnostic imaging / Q000378:metabolism; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D017252:CD3 Complex; D051925:CD79 Antigens; D003287:Contrast Media; D037742:Nanotubes, Carbon; D011956:Receptors, Cell Surface; D013459:Sulfur Hexafluoride