Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme

Year: 2019

Authors: Marino A., Almici E., Migliorin S., Tapeinos C., Battaglini M., Cappello V., Marchetti M., de Vito G., Cicchi R., Pavone FS., Ciofani G.

Autors Affiliation: Istituto Italiano di Tecnologia, Smart Bio-Interfaces, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy; Politecnico di Torino, Department of Mechanical and Aerospace Engineering, Corso Duca degli Abruzzi 24, Torino, 10129, Italy; Scuola Superiore Sant’Anna, The Biorobotics Institute, Viale Rinaldo Piaggio 34, Pontedera, 56025, Italy; Istituto Italiano di Tecnologia, Center for Nanotechnology Innovation, Piazza San Silvestro 12, Pisa, 56127, Italy; European Laboratory for Nonlinear Spectroscopy (LENS), Via Nello Carrara 1, Sesto Fiorentino, 50019, Italy; Università di Firenze, Department of Physics and Astronomy, Via Giovanni Sansone 1, Sesto Fiorentino, 50019, Italy; National Institute of Optics, National Research Council (INO-CNR), Largo Enrico Fermi 6, Firenze, 50125, Italy

Abstract: Major obstacles to the successful treatment of gliolastoma multiforme are mostly related to the acquired resistance to chemotherapy drugs and, after surgery, to the cancer recurrence in correspondence of residual microscopic foci. As innovative anticancer approach, low-intensity electric stimulation represents a physical treatment able to reduce multidrug resistance of cancer and to induce remarkable anti-proliferative effects by interfering with Ca2+ and K+ homeostasis and by affecting the organization of the mitotic spindles. However, to preserve healthy cells, it is utterly important to direct the electric stimuli only to malignant cells. In this work, we propose a nanotechnological approach based on ultrasound-sensitive piezoelectric nanoparticles to remotely deliver electric stimulations to glioblastoma cells. Barium titanate nanoparticles (BINPs) have been functionalized with an antibody against the transferrin receptor (TfR) in order to obtain the dual targeting of blood-brain barrier and of glioblastoma cells. The remote ultrasound-mediated piezo-stimulation allowed to significantly reduce in vitro the proliferation of glioblastoma cells and, when combined with a sub-toxic concentration of temozolomide, induced an increased sensitivity to the chemotherapy treatment and remarkable anti-proliferative and pro-apoptotic effects. (C) 2018 Elsevier Inc. All rights reserved.


Volume: 538      Pages from: 449  to: 461

More Information: This work has received funding from the European Research Council (ERC) under the European Union’s Horizon 2020 research and innovation program (grant agreement N° 709613 , SLaMM).
KeyWords: Barium titanate; Blood; Chemotherapy; Crystallography; Cytology; Diseases; Drug delivery; Electrophysiology; Electrotherapeutics; Nanoparticles; Piezoelectricity; Stimulated emission; Ultrasonics, Antiproliferative effect; Barium titanate nanoparticles; Blood-brain barrier; Chemotherapy treatment; Glioblastoma multiforme; Multidrug resistance; Pro-apoptotic effects; Transferrin receptors, Cells, barium titanate nanoparticle; Ki 67 antigen; nanoparticle; protein p53; temozolomide; transferrin receptor; unclassified drug, antiproliferative activity; Article; biocompatibility; blood brain barrier; cancer therapy; cell nucleus; controlled study; electrostimulation; glioblastoma; human; human cell; immunofluorescence; in vitro study; multimodal imaging; nanotechnology; piezoelectricity; priority journal
DOI: 10.1016/j.jcis.2018.12.014

Citations: 70
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