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

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...

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Published inNanoscale Vol. 7; no. 6; pp. 2336 - 2351
Main Authors Quarta, Alessandra, Bernareggi, Davide, Benigni, Fabio, Luison, Elena, Nano, Giuseppe, Nitti, Simone, Cesta, Maria Candida, Di Ciccio, Luciano, Canevari, Silvana, Pellegrino, Teresa, Figini, Mariangela
Format Journal Article
LanguageEnglish
Published England 14.02.2015
Subjects
Animals
Antibodies - chemistry
Biosensing Techniques
Cell Line, Tumor
Drug Carriers
Drug Delivery Systems
Female
Fluorescent Dyes - chemistry
Humans
Immunoglobulin Fab Fragments - chemistry
Kinetics
Magnetics
Mice
Mice, Nude
Microscopy, Electron, Transmission
Nanomedicine - methods
Nanoparticles - chemistry
Neoplasm Transplantation
Ovarian Neoplasms - immunology
Ovarian Neoplasms - metabolism
Protein Binding
Recombinant Proteins - chemistry
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Summary: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.
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ISSN:2040-3364
2040-3372
DOI:10.1039/c4nr04426f