title: Development of novel anti-Kv 11.1 antibody-conjugated PEG-TiO2nanoparticles for targeting pancreatic ductal adenocarcinoma cells.
abstract: Titanium dioxide (TiO2) has been widely used in many nanotechnology areas including nanomedicine, where it could be proposed for the photodynamic and sonodynamic cancer therapies. However, TiO2nanoformulations have been shown to be toxic for living cells. In this article, we report the development of a new delivery system, based on nontoxic TiO2nanoparticles, further conjugated with a monoclonal antibody against a novel and easily accessible tumor marker, e.g., the Kv 11.1 potassium channel. We synthesized, by simple solvothermal method, dicarboxylic acid-terminated PEG TiO2nanocrystals (PEG-TiO2NPs). Anti-Kv 11.1 monoclonal antibodies (Kv 11.1-Mab) were further linked to the terminal carboxylic acid groups. Proper conjugation was confirmed by X-ray photoelectron spectroscopy analysis. Kv 11.1-Mab-PEG-TiO2NPs efficiently recognized the specific Kv 11.1 antigen, both in vitro and in pancreatic ductal adenocarcinoma (PDAC) cells, which express the Kv 11.1 channel onto the plasma membrane. Both PEG TiO2and Kv 11.1-Mab-PEG-TiO2NPs were not cytotoxic, but only Kv 11.1-Mab-PEG-TiO2NPs were efficiently internalized into PDAC cells. Data gathered from this study may have further applications for the chemical design of nanostructures to be applied for therapeutic purposes in pancreatic cancer.
authors.affiliation: Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Florence, Italy.
authors.forename: Angelica
authors.initials: A
authors.lastname: Sette
authors.affiliation: Laboratoire de Réactivité de Surface, UMR CNRS 7197, Université Pierre & Marie Curie-Paris VI, Site d'Ivry-Le Raphaël, 94200 Ivry-sur-Seine, France.
authors.forename: Jolanda
authors.initials: J
authors.lastname: Spadavecchia
authors.affiliation: Laboratoire de Réactivité de Surface, UMR CNRS 7197, Université Pierre & Marie Curie-Paris VI, Site d'Ivry-Le Raphaël, 94200 Ivry-sur-Seine, France.
authors.forename: Jessem
authors.initials: J
authors.lastname: Landoulsi
authors.affiliation: Laboratoire de Réactivité de Surface, UMR CNRS 7197, Université Pierre & Marie Curie-Paris VI, Site d'Ivry-Le Raphaël, 94200 Ivry-sur-Seine, France.
authors.forename: Sandra
authors.initials: S
authors.lastname: Casale
authors.affiliation: Chimie de la Matière Condensée de Paris, Collège de France, Université Pierre & Marie Curie - Paris VI, 11 place Marcelin Berthelot, Paris, France.
authors.forename: Bernard
authors.initials: B
authors.lastname: Haye
authors.affiliation: Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Florence, Italy ; DI.V.A.L. Toscana srl, Via Madonna del Piano 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Olivia
authors.initials: O
authors.lastname: Crociani
authors.affiliation: Section of Internal Medicine, Department of Experimental and Clinical Medicine, University of Florence, Viale GB Morgagni 50, 50134 Florence, Italy ; DI.V.A.L. Toscana srl, Via Madonna del Piano 6, 50019 Sesto Fiorentino (FI), Italy.
authors.forename: Annarosa
authors.initials: A
authors.lastname: Arcangeli
keywords: Kv 11.1; Nanomedicine; Nanoparticles; PEG–TiO2; Pancreatic cancer; XPS analysis