title: Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Institute of Microbiology, Academy of Sciences of the Czech Republic, VVI, Prague, Czech Republic.
authors.forename: Luca
authors.initials: L
authors.lastname: Vannucci
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Falvo
authors.forename: Manuela
authors.initials: M
authors.lastname: Fornara
authors.forename: Patrizio
authors.initials: P
authors.lastname: Di Micco
authors.forename: Oldrich
authors.initials: O
authors.lastname: Benada
authors.forename: Jiri
authors.initials: J
authors.lastname: Krizan
authors.forename: Jan
authors.initials: J
authors.lastname: Svoboda
authors.forename: Katarina
authors.initials: K
authors.lastname: Hulikova-Capkova
authors.forename: Veronica
authors.initials: V
authors.lastname: Morea
authors.forename: Alberto
authors.initials: A
authors.lastname: Boffi
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ceci
mesh_terms: D000818:Animals; D001052:Apoferritins / Q000737:chemistry; D016503:Drug Delivery Systems; D005456:Fluorescent Dyes / Q000737:chemistry; D019073:HT29 Cells; D006801:Humans; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry / Q000648:ultrastructure; D008297:Male; D008546:Melanoma, Experimental / Q000175:diagnosis*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D046529:Microscopy, Electron, Transmission; D050997:Nanomedicine; D036103:Nanotechnology; D011092:Polyethylene Glycols / Q000737:chemistry; D055550:Protein Stability; D011994:Recombinant Proteins / Q000737:chemistry; D000521:alpha-MSH / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D058185:Magnetite Nanoparticles; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D000521:alpha-MSH; D001052:Apoferritins