title: Active Targeting of Sorafenib: Preparation, Characterization, and In Vitro Testing of Drug-Loaded Magnetic Solid Lipid Nanoparticles.
abstract: Sorafenib is an anticancer drug approved by the Food and Drug Administration for the treatment of hepatocellular and advanced renal carcinoma. The clinical application of sorafenib is promising, yet limited by its severe toxic side effects. The aim of this study is to develop sorafenib-loaded magnetic nanovectors able to enhance the drug delivery to the disease site with the help of a remote magnetic field, thus enabling cancer treatment while limiting negative effects on healthy tissues. Sorafenib and superparamagnetic iron oxide nanoparticles are encapsulated in solid lipid nanoparticles by a hot homogenization technique using cetyl palmitate as lipid matrix. The obtained nanoparticles (Sor-Mag-SLNs) have a sorafenib loading efficiency of about 90% and are found to be very stable in an aqueous environment. Plain Mag-SLNs exhibit good cytocompatibility, whereas an antiproliferative effect against tumor cells (human hepatocarcinoma HepG2) is observed for drug-loaded Sor-Mag-SLNs. The obtained results show that it is possible to prepare stable Sor-Mag-SLNs able to inhibit cancer cell proliferation through the sorafenib cytotoxic action, and to enhance/localize this effect in a desired area thanks to a magnetically driven accumulation of the drug. Moreover, the relaxivity properties observed in water suspensions hold promise for Sor-Mag-SLN tracking through clinical magnetic resonance imaging.
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.|Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
authors.forename: Agostina
authors.initials: A
authors.lastname: Grillone
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.|Scuola Superiore Sant'Anna, The BioRobotics Institute, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
authors.forename: Eugenio Redolfi
authors.initials: ER
authors.lastname: Riva
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
authors.forename: Alessio
authors.initials: A
authors.lastname: Mondini
authors.affiliation: Istituto di Chimica dei Composti OrganoMetallici, Consiglio Nazionale delle Ricerche - CNR, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Forte
authors.affiliation: Istituto di Chimica dei Composti OrganoMetallici, Consiglio Nazionale delle Ricerche - CNR, Via Giuseppe Moruzzi 1, 56124, Pisa, Italy.
authors.forename: Lucia
authors.initials: L
authors.lastname: Calucci
authors.affiliation: INSTM and Department of Chemistry "Ugo Shiff", University of Florence, Via della Lastruccia 3-13, 50019, Sesto Fiorentino, Firenze, Italy.
authors.forename: Claudia
authors.initials: C
authors.lastname: Innocenti
authors.affiliation: Istituto dei Materiali per l'Elettronica e il Magnetismo, Consiglio Nazionale delle Ricerche - CNR, Parco Area delle Scienze 37/A, 43124, Parma, Italy.
authors.forename: Cesar
authors.initials: C
authors.lastname: de Julian Fernandez
authors.affiliation: Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Piazza San Silvestro 12, 56127, Pisa, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Cappello
authors.affiliation: Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation @NEST, Piazza San Silvestro 12, 56127, Pisa, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Gemmi
authors.affiliation: Dipartimento di Medicina Clinica e Sperimentale, Università di Pisa, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Moscato
authors.affiliation: Università di Pisa, Dipartimento di Patologia Chirurgica, Medica, Molecolare e dell'Area Critica, Via Savi 10, 56126, Pisa, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Ronca
authors.affiliation: Unità Operativa di Gastroenterologia e Malattie del Ricambio, Azienda Ospedaliera-Universitaria Pisana, Via Paradisa 2, 56124, Pisa, Italy.
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Sacco
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
authors.forename: Virgilio
authors.initials: V
authors.lastname: Mattoli
authors.affiliation: Istituto Italiano di Tecnologia, Center for Micro-BioRobotics @SSSA, Viale Rinaldo Piaggio 34, 56025, Pontedera, Pisa, Italy.
authors.forename: Gianni
authors.initials: G
authors.lastname: Ciofani
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology; D049109:Cell Proliferation / Q000187:drug effects; D003911:Dextrans / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry*; D056945:Hep G2 Cells; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology; D008279:Magnetic Resonance Imaging; D058185:Magnetite Nanoparticles / Q000737:chemistry*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009536:Niacinamide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000633:toxicity; D010671:Phenylurea Compounds / Q000737:chemistry* / Q000633:toxicity; D000077157:Sorafenib
chemical_list: D000970:Antineoplastic Agents; D003911:Dextrans; D004337:Drug Carriers; D008055:Lipids; D058185:Magnetite Nanoparticles; D010671:Phenylurea Compounds; D009536:Niacinamide; D000077157:Sorafenib; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; C065507:ferumoxides
keywords: HepG2; drug targeting; magnetic nanoparticles; solid lipid nanoparticles; sorafenib