title: A tumor-targeted nanodelivery system to improve early MRI detection of cancer.
abstract: The development of improvements in magnetic resonance imaging (MRI) that would enhance sensitivity, leading to earlier detection of cancer and visualization of metastatic disease, is an area of intense exploration. We have devised a tumor-targeting, liposomal nanodelivery platform for use in gene medicine. This systemically administered nanocomplex has been shown to specifically and efficiently deliver both genes and oligonucleotides to primary and metastatic tumor cells, resulting in significant tumor growth inhibition and even tumor regression. Here we examine the effect on MRI of incorporating conventional MRI contrast agent Magnevist into our anti-transferrin receptor single-chain antibody (TfRscFv) liposomal complex. Both in vitro and in an in vivo orthotopic mouse model of pancreatic cancer, we show increased resolution and image intensity with the complexed Magnevist. Using advanced microscopy techniques (scanning electron microscopy and scanning probe microscopy), we also established that the Magnevist is in fact encapsulated by the liposome in the complex and that the complex still retains its nanodimensional size. These results demonstrate that this TfRscFv-liposome-Magnevist nanocomplex has the potential to become a useful tool in early cancer detection.
authors.affiliation: Georgetown University Medical Center, Washington, DC 20057-1460, USA.
authors.forename: Kathleen F
authors.initials: KF
authors.lastname: Pirollo
authors.forename: John
authors.initials: J
authors.lastname: Dagata
authors.forename: Paul
authors.initials: P
authors.lastname: Wang
authors.forename: Matthew
authors.initials: M
authors.lastname: Freedman
authors.forename: Andras
authors.initials: A
authors.lastname: Vladar
authors.forename: Stanley
authors.initials: S
authors.lastname: Fricke
authors.forename: Lilia
authors.initials: L
authors.lastname: Ileva
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Esther H
authors.initials: EH
authors.lastname: Chang
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D016503:Drug Delivery Systems / Q000379:methods*; D042241:Early Diagnosis; D019786:Gadolinium DTPA; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D007141:Immunoglobulin Fc Fragments / Q000235:genetics / Q000276:immunology; D020014:K562 Cells; D008081:Liposomes / Q000737:chemistry; D008113:Liver Neoplasms / Q000175:diagnosis / Q000556:secondary; D008279:Magnetic Resonance Imaging / Q000379:methods*; D051379:Mice; D008819:Mice, Nude; D008855:Microscopy, Electron, Scanning; D020527:Microscopy, Scanning Probe; D036103:Nanotechnology / Q000379:methods; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000628:therapy*; D011990:Receptors, Transferrin / Q000235:genetics / Q000276:immunology; D023041:Xenograft Model Antitumor Assays
chemical_list: D007141:Immunoglobulin Fc Fragments; D008081:Liposomes; D011990:Receptors, Transferrin; D019786:Gadolinium DTPA