title: Targeting FR-expressing cells in ovarian cancer with Fab-functionalized nanoparticles: a full study to provide the proof of principle from in vitro to in vivo.
abstract: Efficient targeting in tumor therapies is still an open issue: systemic biodistribution and poor specific accumulation of drugs weaken efficacy of treatments. Engineered nanoparticles are expected to bring benefits by allowing specific delivery of drug to the tumor or acting themselves as localized therapeutic agents. In this study we have targeted epithelial ovarian cancer with inorganic nanoparticles conjugated to a human antibody fragment against the folate receptor over-expressed on cancer cells. The conjugation approach is generally applicable. Indeed several types of nanoparticles (either magnetic or fluorescent) were engineered with the fragment, and their biological activity was preserved as demonstrated by biochemical methods in vitro. In vivo studies with mice bearing orthotopic and subcutaneous tumors were performed. Elemental and histological analyses showed that the conjugated magnetic nanoparticles accumulated specifically and were retained at tumor sites longer than the non-conjugated nanoparticles.
authors.affiliation: Nanoscience Institute of CNR, National Nanotechnology Laboratory, via Arnesano, 73100, Lecce, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Quarta
authors.forename: Davide
authors.initials: D
authors.lastname: Bernareggi
authors.forename: Fabio
authors.initials: F
authors.lastname: Benigni
authors.forename: Elena
authors.initials: E
authors.lastname: Luison
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Nano
authors.forename: Simone
authors.initials: S
authors.lastname: Nitti
authors.forename: Maria Candida
authors.initials: MC
authors.lastname: Cesta
authors.forename: Luciano
authors.initials: L
authors.lastname: Di Ciccio
authors.forename: Silvana
authors.initials: S
authors.lastname: Canevari
authors.forename: Teresa
authors.initials: T
authors.lastname: Pellegrino
authors.forename: Mariangela
authors.initials: M
authors.lastname: Figini
mesh_terms: D000818:Animals; D000906:Antibodies / Q000737:chemistry; D015374:Biosensing Techniques; D045744:Cell Line, Tumor; D004337:Drug Carriers; D016503:Drug Delivery Systems; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry; D006801:Humans; D007140:Immunoglobulin Fab Fragments / Q000737:chemistry*; D007700:Kinetics; D008280:Magnetics; D051379:Mice; D008819:Mice, Nude; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine / Q000379:methods; D053758:Nanoparticles / Q000737:chemistry*; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000276:immunology* / Q000378:metabolism*; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry
chemical_list: D000906:Antibodies; D004337:Drug Carriers; D005456:Fluorescent Dyes; D007140:Immunoglobulin Fab Fragments; D011994:Recombinant Proteins