Directing cancer cell fate with wireless barium titanate@PEDOT nanoparticles to control bioelectricity

Abstract Cancer cells exhibit unique bioelectrical properties, yet therapeutic strategies exploiting these are still lacking. Herein, we merge a nanobioelectronic system comprising of a barium titanate nanoparticle core and a poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs) with cancer cells to modulate bioelectricity. We hypothesize that the BTO@PEDOT NPs act as a nanoantenna, transducing a mechanical input provided by external ultrasound (US) stimulation into an electrical output, capable of interfering with the bioelectronic circuitry of the human breast cancer cell lines, MCF-7 and MDA-MB-231. Upon US stimulation the viability of MCF-7 and MDA-MB-231 treated with 200 µg mL-1 BTO@PEDOT NPs reduced significantly to 31% and 24%, respectively, while healthy human mammary fibroblasts were unaffected by the treatment (94% viability). The treatment increased ROS levels and intracellular Ca2+ concentrations, thus promoting apoptosis. These findings underscore the potential of nanobioelectronic systems as an emerging and promising strategy for cancer intervention with no impact on healthy cells.