Wireless Stimulation of Barium Titanate@PEDOT Nanoparticles Toward Bioelectrical Modulation in Cancer

Abstract

Cancer cells possess distinct bioelectrical properties, yet therapies leveraging these characteristics remain underexplored. Herein, we introduce an innovative nanobioelectronic system combining a piezoelectric barium titanate nanoparticle core with a conducting poly(3,4-ethylenedioxythiophene) shell (BTO@PEDOT NPs), designed to modulate cancer cell bioelectricity through noninvasive, wireless stimulation. Our hypothesis is that acting as nanoantennas, BTO@PEDOT NPs convert mechanical inputs provided by ultrasound (US) into electrical signals, capable of interfering with the bioelectronic circuitry of two human breast cancer cell lines, MCF-7 and MDA-MB-231. Upon US stimulation, the viability of MCF-7 and MDA-MB-231 cells treated with 200 μg mL^-1 BTO@PEDOT NPs and US reduced significantly to 31% and 24%, respectively, while healthy human mammary fibroblasts (HMF) were unaffected by the treatment. Subsequent assays shed light on how this approach could interact with cell's bioelectrical mechanisms, namely, by increasing intracellular reactive oxygen species (ROS) and calcium concentrations. Furthermore, this system was able to polarize cancer cell membranes, halting their cell cycle and potentially harnessing their tumorigenic characteristics. These findings underscore the crucial role of bioelectricity in cancer progression and highlight the potential of nanobioelectronic systems as an emerging and promising strategy for cancer intervention.

Keywords: breast cancer; cancer bioelectricity; multifunctional nanoparticles; nanobioelectronics; ultrasound stimulation; wireless stimulation.