title: Cisplatin encapsulation within a ferritin nanocage: a high-resolution crystallographic study.
abstract: Cisplatin (CDDP) can be encapsulated within the central cavity of reconstituted (apo)ferritin, (A)Ft, to form a drug-loaded protein of potential great interest for targeted cancer treatments. In this study, the interactions occurring between cisplatin and native horse spleen Ft in CDDP-encapsulated AFt are investigated by high-resolution X-ray crystallography. A protein bound Pt center is unambiguously identified in AFt subunits by comparative analysis of difference Fourier electron density maps and of anomalous dispersion data. Indeed, a [Pt(NH3)2H2O](2+) fragment is found coordinated to the His132 residue located on the inner surface of the large AFt spherical cage. Remarkably, Pt binding does not alter the overall physicochemical features (shape, volume, polarity/hydrophobicity and electrostatic potential) of the outer surface of the AFt nanocage. CDDP-encapsulated AFt appears to be an ideal nanocarrier for CDDP delivery to target sites, as it possesses high biocompatibility and can be internalized by receptor mediated endocytosis, thus carrying the drug to tumor tissue with higher selectivity than free CDDP.
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy. antonello.merlino@unina.it.
authors.forename: Nicola
authors.initials: N
authors.lastname: Pontillo
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy. antonello.merlino@unina.it.
authors.forename: Francesca
authors.initials: F
authors.lastname: Pane
authors.affiliation: Department of Chemistry, University of Florence, Via della Lastruccia 3, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Messori
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy. antonello.merlino@unina.it.
authors.forename: Angela
authors.initials: A
authors.lastname: Amoresano
authors.affiliation: Department of Chemical Sciences, University of Naples Federico II, Complesso Universitario di Monte Sant'Angelo, Via Cintia, I-80126, Napoli, Italy. antonello.merlino@unina.it and CNR Institute of Biostructures and Bioimages, Via Mezzocannone 16, I-80126, Napoli, Italy.
authors.forename: Antonello
authors.initials: A
authors.lastname: Merlino
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D002945:Cisplatin / Q000737:chemistry*; D018360:Crystallography, X-Ray; D005293:Ferritins / Q000737:chemistry*; D015394:Molecular Structure; D049329:Nanostructures
chemical_list: D000970:Antineoplastic Agents; D005293:Ferritins; D002945:Cisplatin