title: Biotin-Containing Reduced Graphene Oxide-Based Nanosystem as a Multieffect Anticancer Agent: Combining Hyperthermia with Targeted Chemotherapy.
abstract: Among the relevant properties of graphene derivatives, their ability of acting as an energy-converting device so as to produce heat (i.e., thermoablation and hyperthermia) was more recently taken into account for the treatment of solid tumors. In this pioneering study, for the first time, the in vitro RGO-induced hyperthermia was assessed and combined with the stimuli-sensitive anticancer effect of a biotinylated inulin-doxorubicin conjugate (CJ-PEGBT), hence, getting to a nanosystem endowed with synergic anticancer effects and high specificity. CJ-PEGBT was synthesized by linking pentynoic acid and citraconic acid to inulin. The citraconylamide pendants, used as pH reversible spacer, were exploited to further conjugate doxorubicin, whereas the alkyne moiety was orthogonally functionalized with an azido PEG-biotin derivative by copper(II) catalyzed 1,3-dipolar cycloaddition. DSC measures, AFM, and UV spectrophotometry were employed to systematically investigate adsorption of CJ-PEGBT onto RGO and its physicochemical stability in aqueous media, demonstrating that a stable π-staked nanosystem can be obtained. In vitro tests using cancer breast cells (MCF-7) showed the ability of the RGO/CJ-PEGBT of efficiently killing cancer cells both via a selective laser beam thermoablation and hyperthermia-triggered chemotherapy. If compared with the nonbiotinylated nanosystem, including virgin RGO and the free conjugate, RGO/CJ-PEGBT is endowed with a smart combination of properties which warrant potential as an anticancer nanomedicine.
authors.affiliation: Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo , Via Archirafi, 32 90123 Palermo, Italy.
authors.forename: Nicolò
authors.initials: N
authors.lastname: Mauro
authors.affiliation: Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo , Via Archirafi, 32 90123 Palermo, Italy.
authors.forename: Cinzia
authors.initials: C
authors.lastname: Scialabba
authors.affiliation: Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo , Via Archirafi, 32 90123 Palermo, Italy.
authors.forename: Gennara
authors.initials: G
authors.lastname: Cavallaro
authors.affiliation: Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo , Via Archirafi, 32 90123 Palermo, Italy.|Mediterranean Center for Human Advanced Biotechnologies (Med-Chab), Viale delle Scienze Ed.18, 90128 Palermo, Italy.
authors.forename: Mariano
authors.initials: M
authors.lastname: Licciardi
authors.affiliation: Laboratory of Biocompatible Polymers, Department of "Scienze e Tecnologie Biologiche, Chimiche e Farmaceutiche" (STEBICEF), University of Palermo , Via Archirafi, 32 90123 Palermo, Italy.|Mediterranean Center for Human Advanced Biotechnologies (Med-Chab), Viale delle Scienze Ed.18, 90128 Palermo, Italy.
authors.forename: Gaetano
authors.initials: G
authors.lastname: Giammona
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology; D001710:Biotin / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy*; D004317:Doxorubicin / Q000737:chemistry / Q000494:pharmacology; D016503:Drug Delivery Systems / Q000379:methods*; D005260:Female; D006108:Graphite / Q000737:chemistry*; D006801:Humans; D006863:Hydrogen-Ion Concentration; D006979:Hyperthermia, Induced; D007444:Inulin / Q000737:chemistry; D061986:MCF-7 Cells; D053758:Nanoparticles / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D001710:Biotin; D006108:Graphite; D004317:Doxorubicin; D007444:Inulin