SELECTIVE TARGETING BY PEG-MASKED FERRITIN-BASED MULTIFUNCTIONAL
NANOPARTICLES
M. Carbo1, E. Falvo2, P.M. Lacal3, G. Carpinelli4, S. Cecchetti4, L. Vannucci5, M. Fornara6,
P. Di Micco2, G. Zambruno1, A. Boffi6, C.M. Failla1, V. Morea2, P. Ceci2
1
Laboratory of Molecular and Cell Biology and 3Laboratory of Molecular Oncology, IDI-IRCCS, Rome, Italy; 2CNR
Institute of Molecular Biology and Pathology and 6Department of Biochemical Sciences “A. Rossi Fanelli”, University
"La Sapienza", Rome, Italy; 4Istituto Superiore di Sanità (ISS), Department of Cell Biology and Neuroscience, Rome,
Italy; 5Institute of Microbiology, Department of Immunology and Gnotobiology, Laboratory of Natural Cell Immunity,
Prague, Czech Republic.
Nanoparticle-based systems are promising for the development of imaging and therapeutic agents.
Targeted delivery of nanoparticles requires an accurate system design. We developed nanoparticle
constructs (NPs) based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical
assembly of 24 subunits enclosing a hollow cavity.
HFt-based NPs were produced using both genetic engineering and chemical modifications to impart
functionalities such as: the α-melanocyte-stimulating hormone peptide, as a melanoma-targeting
moiety, or a recently-developed peptide, named P12, as a α5β1 integrin-targeting agent;
polyethylene glycol molecules as stabilizing moieties; rhodamine fluorophores and magnetic
resonance imaging agents for detection. The produced constructs were characterized by a number of
physicochemical techniques, and assayed for selective melanoma or endothelial cell-targeting in
vitro and in vivo.
HFt-based NPs were specifically taken up by the targeted cells in vitro. Moreover, experiments in
melanoma-bearing mice indicated that these constructs had a good tumor-targeting and vesseltargeting profile in vivo.