title: Evidence for in vivo macrophage mediated tumor uptake of paramagnetic/fluorescent liposomes.
abstract: Dysprosium (Dy)-loaded liposomes act as excellent T(2)-susceptibility agents at high magnetic field strength. The R(2)-enhancement increases with the size of the liposomes and the concentration of entrapped paramagnetic metal complexes. Neuro-2a tumor cells are readily labeled when Dy-loaded liposomes, suitably functionalized with glutamine residues (Gln), are added to the culture medium as glutamine receptors are highly expressed in such proliferating tumor cells. By using fluorescent liposomes doped with fluorescent dyes (either incorporated in the membrane or included in the inner cavity), confocal microscopy experiments showed that targeted liposomes are taken up much more avidly than non-targeted vesicles. In vivo studies showed that glutamine-functionalized and non-functionalized liposomes accumulate in the tumor region to a similar extent. Confocal images of the excised tumor showed extensive co-localization of liposomes and macrophages in both cases. It is suggested that the loss of tumor specificity, shown by Gln-functionalized liposomes in vivo, has to be associated with the efficient removal of liposomes operated by the RES (reticulo endoplasmatic system) or tumor associated macrophages.
authors: Department of Chemistry, IFM and Molecular Imaging Center, University of Torino, Via P. Giuria 7, I-10125 Torino, Italy.
authors: Daniela Delli
authors: DD
authors: Castelli
authors: Enzo
authors: E
authors: Terreno
authors: Claudia
authors: C
authors: Cabella
authors: Linda
authors: L
authors: Chaabane
authors: Stefania
authors: S
authors: Lanzardo
authors: Lorenzo
authors: L
authors: Tei
authors: Massimo
authors: M
authors: Visigalli
authors: Silvio
authors: S
authors: Aime
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003287:Contrast Media / Q000737:chemistry / Q000378:metabolism; D004337:Drug Carriers / Q000737:chemistry / Q000378:metabolism; D004419:Dysprosium / Q000737:chemistry / Q000378:metabolism; D005456:Fluorescent Dyes / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008081:Liposomes / Q000737:chemistry / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000378:metabolism*; D008279:Magnetic Resonance Imaging; D008280:Magnetics; D008297:Male; D051379:Mice; D015394:Molecular Structure; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D019906:Nuclear Magnetic Resonance, Biomolecular; D010743:Phospholipids / Q000737:chemistry
chemical_list: D003287:Contrast Media; D004337:Drug Carriers; D005456:Fluorescent Dyes; D008081:Liposomes; D010743:Phospholipids; D004419:Dysprosium