title: Ferri-liposomes as an MRI-visible drug-delivery system for targeting tumours and their microenvironment.
abstract: The tumour microenvironment regulates tumour progression and the spread of cancer in the body. Targeting the stromal cells that surround cancer cells could, therefore, improve the effectiveness of existing cancer treatments. Here, we show that magnetic nanoparticle clusters encapsulated inside a liposome can, under the influence of an external magnet, target both the tumour and its microenvironment. We use the outstanding T2 contrast properties (r2=573-1,286 s(-1) mM(-1)) of these ferri-liposomes, which are ∼95 nm in diameter, to non-invasively monitor drug delivery in vivo. We also visualize the targeting of the tumour microenvironment by the drug-loaded ferri-liposomes and the uptake of a model probe by cells. Furthermore, we used the ferri-liposomes to deliver a cathepsin protease inhibitor to a mammary tumour and its microenvironment in a mouse, which substantially reduced the size of the tumour compared with systemic delivery of the same drug.
authors.affiliation: Department of Biochemistry and Molecular and Structural Biology, Jozef Stefan Institute, SI-1000 Ljubljana, Slovenia.
authors.forename: Georgy
authors.initials: G
authors.lastname: Mikhaylov
authors.forename: Ursa
authors.initials: U
authors.lastname: Mikac
authors.forename: Anna A
authors.initials: AA
authors.lastname: Magaeva
authors.forename: Volya I
authors.initials: VI
authors.lastname: Itin
authors.forename: Evgeniy P
authors.initials: EP
authors.lastname: Naiden
authors.forename: Ivan
authors.initials: I
authors.lastname: Psakhye
authors.forename: Liane
authors.initials: L
authors.lastname: Babes
authors.forename: Thomas
authors.initials: T
authors.lastname: Reinheckel
authors.forename: Christoph
authors.initials: C
authors.lastname: Peters
authors.forename: Robert
authors.initials: R
authors.lastname: Zeiser
authors.forename: Matthew
authors.initials: M
authors.lastname: Bogyo
authors.forename: Vito
authors.initials: V
authors.lastname: Turk
authors.forename: Sergey G
authors.initials: SG
authors.lastname: Psakhye
authors.forename: Boris
authors.initials: B
authors.lastname: Turk
authors.forename: Olga
authors.initials: O
authors.lastname: Vasiljeva
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002478:Cells, Cultured; D016503:Drug Delivery Systems / Q000379:methods*; D006801:Humans; D008081:Liposomes / Q000737:chemistry* / Q000648:ultrastructure; D008279:Magnetic Resonance Imaging; D059346:Magnets / Q000737:chemistry*; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D009369:Neoplasms / Q000188:drug therapy; D014407:Tumor Cells, Cultured; D059016:Tumor Microenvironment
chemical_list: D000970:Antineoplastic Agents; D008081:Liposomes