  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.
