title: A smart platform for hyperthermia application in cancer treatment: cobalt-doped ferrite nanoparticles mineralized in human ferritin cages.
abstract: Magnetic nanoparticles, MNPs, mineralized within a human ferritin protein cage, HFt, can represent an appealing platform to realize smart therapeutic agents for cancer treatment by drug delivery and magnetic fluid hyperthermia, MFH. However, the constraint imposed by the inner diameter of the protein shell (ca. 8 nm) prevents its use as heat mediator in MFH when the MNPs comprise pure iron oxide. In this contribution, we demonstrate how this limitation can be overcome through the controlled doping of the core with small amount of Co(II). Highly monodisperse doped iron oxide NPs with average size of 7 nm are mineralized inside a genetically modified variant of HFt, carrying several copies of α-melanocyte-stimulating hormone peptide, which has already been demonstrated to have excellent targeting properties toward melanoma cells. HFt is also conjugated to poly(ethylene glycol) molecules to increase its in vivo stability. The investigation of hyperthermic properties of HFt-NPs shows that a Co doping of 5% is enough to strongly enhance the magnetic anisotropy and thus the hyperthermic efficiency with respect to the undoped sample. In vitro tests performed on B16 melanoma cell line demonstrate a strong reduction of the cell viability after treatment with Co doped HFt-NPs and exposure to the alternating magnetic field. Clear indications of an advanced stage of apoptotic process is also observed from immunocytochemistry analysis. The obtained data suggest this system represents a promising candidate for the development of a protein-based theranostic nanoplatform.
authors.affiliation: INSTM and Dipartimento di Chimica "U. Schiff", Università degli Studi di Firenze , via della Lastruccia 3, I-50019 Sesto Fiorentino, Italy.
authors.forename: Elvira
authors.initials: E
authors.lastname: Fantechi
authors.forename: Claudia
authors.initials: C
authors.lastname: Innocenti
authors.forename: Matteo
authors.initials: M
authors.lastname: Zanardelli
authors.forename: Maria
authors.initials: M
authors.lastname: Fittipaldi
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Falvo
authors.forename: Miriam
authors.initials: M
authors.lastname: Carbo
authors.forename: Valbona
authors.initials: V
authors.lastname: Shullani
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Di Cesare Mannelli
authors.forename: Carla
authors.initials: C
authors.lastname: Ghelardini
authors.forename: Anna Maria
authors.initials: AM
authors.lastname: Ferretti
authors.forename: Alessandro
authors.initials: A
authors.lastname: Ponti
authors.forename: Claudio
authors.initials: C
authors.lastname: Sangregorio
authors.forename: Pierpaolo
authors.initials: P
authors.lastname: Ceci
mesh_terms: D000818:Animals; D016880:Anisotropy; D045744:Cell Line, Tumor; D002470:Cell Survival; D003035:Cobalt / Q000737:chemistry*; D004337:Drug Carriers; D005290:Ferric Compounds / Q000737:chemistry*; D005293:Ferritins / Q000737:chemistry*; D006801:Humans; D006979:Hyperthermia, Induced / Q000379:methods*; D008280:Magnetics; D008545:Melanoma / Q000188:drug therapy; D008546:Melanoma, Experimental; D053768:Metal Nanoparticles / Q000737:chemistry*; D051379:Mice; D036103:Nanotechnology / Q000379:methods; D009369:Neoplasms / Q000188:drug therapy / Q000628:therapy*; D010455:Peptides / Q000737:chemistry; D000521:alpha-MSH / Q000737:chemistry
chemical_list: D004337:Drug Carriers; D005290:Ferric Compounds; D010455:Peptides; C001215:ferrite; C000499:ferric oxide; D003035:Cobalt; D000521:alpha-MSH; D005293:Ferritins