Piezoelectric barium titanate nanostimulators for the treatment of glioblastoma multiforme

• Published in: Journal of colloid and interface science 2019-03, Vol.538, p.449-461
• Main Authors: Marino, Attilio, Almici, Enrico, Migliorin, Simone, Tapeinos, Christos, Battaglini, Matteo, Cappello, Valentina, Marchetti, Marco, de Vito, Giuseppe, Cicchi, Riccardo, Pavone, Francesco Saverio, Ciofani, Gianni
• Format: Article
• Language: English
• Subjects: antibodies; Antineoplastic Agents, Alkylating - chemistry; Antineoplastic Agents, Alkylating - pharmacology; apoptosis; Apoptosis - drug effects; Barium Compounds - chemistry; barium titanate; Barium titanate nanoparticles; Blood-brain barrier; Blood-Brain Barrier - drug effects; Brain Neoplasms - drug therapy; Brain Neoplasms - pathology; calcium; Cell Proliferation - drug effects; Drug Screening Assays, Antitumor; drug therapy; drugs; glioblastoma; Glioblastoma - drug therapy; Glioblastoma - pathology; Glioblastoma multiforme; homeostasis; Humans; multiple drug resistance; nanoparticles; Nanoparticles - chemistry; Nanotechnology; Piezoelectricity; potassium; surgery; Temozolomide - chemistry; Temozolomide - pharmacology; Titanium - chemistry; transferrin receptors; Tumor Cells, Cultured; Wireless stimulation
• ISSN: 0021-9797; 1095-7103; 1095-7103
• DOI: 10.1016/j.jcis.2018.12.014

[Display omitted] 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 (BTNPs) 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.