title: In vivo monitoring of liposomal release in tumours following ultrasound stimulation.
abstract: Dioeleoylphosphatidylethanolamine (DOPE)-based liposomes were recently reported as a new class of liposomes for ultrasound (US)-mediated drug delivery. The liposomes showed both high stability and in vitro US-mediated drug release (sonosensitivity). In the current study, in vivo proof-of-principle of US triggered release in tumoured mice was demonstrated using optical imaging. Confocal non-thermal US was used to deliver cavitation to tumours in a well-controlled manner. To detect in vivo release, the near infrared fluorochrome Al (III) Phthalocyanine Chloride Tetrasulphonic acid (AlPcS₄) was encapsulated into both DOPE-based liposomes and control liposomes based on hydrogenated soy phosphatidylcholine (HSPC). Encapsulation causes concentration dependent quenching of fluorescence that is recovered upon AlPcS₄ release from the liposomes. Exposure of tumours to US resulted in a significant increase in fluorescence in mice administered with DOPE-based liposomes, but no change in the mice treated with HSPC-based liposomes. Thus, DOPE-based liposomes showed superior sonosensitivity compared to HSPC-based liposomes in vivo.
authors.affiliation: Epitarget AS, Oslo, Norway.
authors.forename: Tove J
authors.initials: TJ
authors.lastname: Evjen
authors.forename: Eirik
authors.initials: E
authors.lastname: Hagtvet
authors.forename: Alexei
authors.initials: A
authors.lastname: Moussatov
authors.forename: Sibylla
authors.initials: S
authors.lastname: Røgnvaldsson
authors.forename: Jean-Louis
authors.initials: JL
authors.lastname: Mestas
authors.forename: R Andrew
authors.initials: RA
authors.lastname: Fowler
authors.forename: Cyril
authors.initials: C
authors.lastname: Lafon
authors.forename: Esben A
authors.initials: EA
authors.lastname: Nilssen
mesh_terms: D000535:Aluminum / Q000737:chemistry; D000818:Animals; D002712:Chlorides / Q000737:chemistry; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D007211:Indoles / Q000737:chemistry; D054833:Isoindoles; D008081:Liposomes / Q000737:chemistry* / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D010714:Phosphatidylethanolamines / Q000737:chemistry*; D013451:Sulfonic Acids / Q000737:chemistry; D013997:Time Factors; D014465:Ultrasonics
chemical_list: C410262:1,2-dioleoyl-glycero-3-phosphatidyl ethanolamine; D002712:Chlorides; D005456:Fluorescent Dyes; D007211:Indoles; D054833:Isoindoles; D008081:Liposomes; D010714:Phosphatidylethanolamines; D013451:Sulfonic Acids; D000535:Aluminum; C013647:phthalocyanine