title: Direct chemical grafted curcumin on halloysite nanotubes as dual-responsive prodrug for pharmacological applications.
abstract: Covalently functionalized halloysite nanotubes (HNTs) were successfully employed as dual-responsive nanocarriers for curcumin (Cur). Particularly, we synthesized HNT-Cur prodrug with a controlled curcumin release on dependence of both intracellular glutathione (GSH) and pH conditions. In order to obtain HNT-Cur produgs, halloysite was firstly functionalized with cysteamine through disulphide linkage. Afterwards, curcumin molecules were chemically conjugated to the amino end groups of halloysite via Schiff's base formation. The successful functionalization of halloysite was proved by thermogravimetric analysis, FT-IR spectroscopy, dynamic light scattering and scanning electron microscopy. Experimental data confirmed the presence of curcumin on HNT external surface. Moreover, we investigated the kinetics of curcumin release by UV-vis spectroscopy, which highlighted that HNT-Cur prodrug possesses dual stimuli-responsive ability upon exposure to GSH-rich or acidic environment. In vitro antiproliferative and antioxidant properties of HNT-Cur prodrug were studied with the aim to explore their potential applications in pharmaceutics. This work puts forward an efficient strategy to prepare halloysite based nanocarriers with controlled drug delivery capacity through direct chemical grafting with stimuli-responsive linkage.
authors.affiliation: Dipartimento STEBICEF, Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Massaro
authors.affiliation: Dipartimento di Chimica "Giacomo Ciamician", Via S.Giacomo 11, Bologna, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Amorati
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Cavallaro
authors.affiliation: Dipartimento di Chimica "Giacomo Ciamician", Via S.Giacomo 11, Bologna, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Guernelli
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy. Electronic address: giuseppe.lazzara@unipa.it.
authors.forename: G
authors.initials: G
authors.lastname: Lazzara
authors.affiliation: Dipartimento di Fisica e Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Milioto
authors.affiliation: Dipartimento STEBICEF, Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy.
authors.forename: R
authors.initials: R
authors.lastname: Noto
authors.affiliation: Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'Alessandro", Area Funzionale di Farmacologia, Università di Palermo, Via del Vespro 129, 90127 Palermo, Italy.
authors.forename: P
authors.initials: P
authors.lastname: Poma
authors.affiliation: Dipartimento STEBICEF, Sez. Chimica, Università degli Studi di Palermo, Viale delle Scienze, Parco d'Orleans II, Ed. 17, 90128 Palermo, Italy. Electronic address: serena.riela@unipa.it.
authors.forename: S
authors.initials: S
authors.lastname: Riela
mesh_terms: D000538:Aluminum Silicates; D000970:Antineoplastic Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D000077215:Clay; D003474:Curcumin / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D004337:Drug Carriers / Q000737:chemistry; D016166:Free Radical Scavengers / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008855:Microscopy, Electron, Scanning; D043942:Nanotubes / Q000737:chemistry* / Q000648:ultrastructure; D010084:Oxidation-Reduction; D011355:Prodrugs / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology
chemical_list: D000538:Aluminum Silicates; D000970:Antineoplastic Agents; D004337:Drug Carriers; D016166:Free Radical Scavengers; D011355:Prodrugs; D003474:Curcumin; D000077215:Clay
keywords: Antioxidant properties; Antiproliferative activity; Curcumin; Halloysite nanotubes; Prodrug