title: MRI contrast variation of thermosensitive magnetoliposomes triggered by focused ultrasound: a tool for image-guided local drug delivery.
abstract: Improved drug delivery control during chemotherapy has the potential to increase the therapeutic index. MRI contrast agent such as iron oxide nanoparticles can be co-encapsulated with drugs in nanocarrier liposomes allowing their tracking and/or visualization by MRI. Furthermore, the combination of a thermosensitive liposomal formulation with an external source of heat such as high intensity focused ultrasound guided by MR temperature mapping allows the controlled local release of the content of the liposome. MRI-guided high-intensity focused ultrasound (HIFU), in combination represents a noninvasive technique to generate local hyperthermia for drug release. In this study we used ultrasmall superparamagnetic iron oxide nanoparticles (USPIO) encapsulated in thermosensitive liposomes to obtain thermosensitive magnetoliposomes (TSM). The transverse and longitudinal relaxivities of this MRI contrast agent were measured upon TSM membrane phase transition in vitro using a water bath or HIFU. The results showed significant differences for MRI signal enhancement and relaxivities before and after heating, which were absent for nonthermosensitive liposomes and free nanoparticles used as controls. Thus, incorporation of USPIO as MRI contrast agents into thermosensitive liposomes should, besides TSM tumor accumulation monitoring, allow the visualization of TSM membrane phase transition upon temperature elevation. In conclusion, HIFU under MR image guidance in combination with USPIO-loaded thermosensitive liposomes as drug delivery system has the potential for a better control of drug delivery and to increase the drug therapeutic index.
authors.affiliation: Imaging Division, University Medical Center Utrecht, Heidelberglaan 100, 3584 CX, Utrecht, The Netherlands.
authors.forename: Cyril
authors.initials: C
authors.lastname: Lorenzato
authors.forename: Alexandru
authors.initials: A
authors.lastname: Cernicanu
authors.forename: Marie-Edith
authors.initials: ME
authors.lastname: Meyre
authors.forename: Matthieu
authors.initials: M
authors.lastname: Germain
authors.forename: Agnès
authors.initials: A
authors.lastname: Pottier
authors.forename: Laurent
authors.initials: L
authors.lastname: Levy
authors.forename: Baudouin Denis
authors.initials: BD
authors.lastname: de Senneville
authors.forename: Clemens
authors.initials: C
authors.lastname: Bos
authors.forename: Chrit
authors.initials: C
authors.lastname: Moonen
authors.forename: Pierre
authors.initials: P
authors.lastname: Smirnov
mesh_terms: D003287:Contrast Media / Q000737:chemistry / Q000528:radiation effects; D003692:Delayed-Action Preparations / Q000737:chemistry* / Q000528:radiation effects*; D006358:Hot Temperature; D008081:Liposomes / Q000737:chemistry* / Q000528:radiation effects; D060526:Magnetic Fields; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles / Q000737:chemistry* / Q000528:radiation effects*; D008422:Materials Testing; D013010:Sonication / Q000379:methods*; D013016:Sound
chemical_list: D003287:Contrast Media; D003692:Delayed-Action Preparations; D008081:Liposomes; D058185:Magnetite Nanoparticles