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Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles
L. Vannucci, E. Falvo, M. Fornara, P. Di Micco, O. Benada, J. Krizan, J. Svoboda, K. Hulikova-Capkova, V. Morea, A. Boffi, P. Ceci
Language English Country New Zealand
Document type Journal Article, Research Support, Non-U.S. Gov't
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PubMed
22619508
DOI
10.2147/ijn.s28242
Knihovny.cz E-resources
- MeSH
- alpha-MSH chemistry diagnostic use MeSH
- Apoferritins chemistry MeSH
- HT29 Cells MeSH
- Fluorescent Dyes chemistry diagnostic use MeSH
- Microscopy, Confocal MeSH
- Drug Delivery Systems MeSH
- Humans MeSH
- Magnetic Resonance Imaging MeSH
- Magnetite Nanoparticles chemistry diagnostic use ultrastructure MeSH
- Melanoma, Experimental diagnosis MeSH
- Mice, Inbred C57BL MeSH
- Mice MeSH
- Nanomedicine MeSH
- Nanotechnology MeSH
- Polyethylene Glycols chemistry MeSH
- Recombinant Proteins chemistry MeSH
- Protein Stability MeSH
- Microscopy, Electron, Transmission MeSH
- Animals MeSH
- Check Tag
- Humans MeSH
- Male MeSH
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
BACKGROUND: Nanoparticle-based systems are promising for the development of imaging and therapeutic agents. The main advantage of nanoparticles over traditional systems lies in the possibility of loading multiple functionalities onto a single molecule, which are useful for therapeutic and/or diagnostic purposes. These functionalities include targeting moieties which are able to recognize receptors overexpressed by specific cells and tissues. However, targeted delivery of nanoparticles requires an accurate system design. We present here a rationally designed, genetically engineered, and chemically modified protein-based nanoplatform for cell/tissue-specific targeting. METHODS: Our nanoparticle constructs were based on the heavy chain of the human protein ferritin (HFt), a highly symmetrical assembly of 24 subunits enclosing a hollow cavity. HFt-based nanoparticles were produced using both genetic engineering and chemical functionalization methods to impart several functionalities, ie, the α-melanocyte-stimulating hormone peptide as a melanoma-targeting moiety, stabilizing and HFt-masking polyethylene glycol molecules, rhodamine fluorophores, and magnetic resonance imaging agents. The constructs produced were extensively characterized by a number of physicochemical techniques, and assayed for selective melanoma-targeting in vitro and in vivo. RESULTS: Our HFt-based nanoparticle constructs functionalized with the α-melanocyte-stimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo. CONCLUSION: By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available.
Center for Life Nano Science at Sapienza Italian Institute of Technology Rome Italy
Department of Biochemical Sciences “A Rossi Fanelli” University of Rome “Sapienza”
Institute of Microbiology Academy of Sciences of the Czech Republic VVI Prague Czech Republic
National Research Council of Italy Institute of Molecular Biology and Pathology
Regina Elena Cancer Institute Pharmacokinetic Pharmacogenomic Unit
References provided by Crossref.org
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