Wireless Ultrasonic-Powered Tumor Treating Fields via BaTiO₃ Pyramid Receivers for Cancer Treatment

Introduction: : Tumor Treating Fields (TTF) has emerged as a promising treatment modality by disrupting cancer cell mitosis through alternating electric fields. While efficacious, the current TTF instrument, i.e., a wearable coil patch, hinders wide adoption for treating deep-seated tumors due to coarse spatial resolution, field attenuation, limited control over field direction, and poor patient compliance. To address these challenges, we have developed a wireless ultrasonic-powered TTF delivery platform basis of barium titanate (BaTiO₃) nanoparticle-based pyramid receivers (Fig. 1). These miniature receivers, when activated by focused ultrasound, generate FDA-equivalent electric fields in a localized manner for disrupting cancer cell division. This study aims to demonstrate the feasibility of wireless ultrasonic-powered TTF delivery and evaluate its cytotoxic effect on the highly aggressive brain tumor, glioblastoma (GBM) cells, through proof-of-concept in vitro experiments.

Materials and

Methods: : Pyramid-shaped ultrasonic receivers were fabricated using 500 nm BaTiO₃ nanoparticles. Initially, the nanoparticles were thoroughly dried to remove moisture and then molded into pyramid shapes using wax molds. These molded structures were sintered in a high-temperature furnace at 1400°C for 180 minutes to achieve dense, mechanically stable pyramids. Following sintering, conductive silver epoxy was applied to the top and base, and copper wires were affixed for electrical connections. To enhance piezoelectric properties, the pyramids were poled at 110°C by applying a high electric field (~2.2 kV/mm) in a silicone oil bath to align the dipole moments.
For wireless powering, a focused ultrasonic transducer operating at 670 kHz was positioned at the optimal focal distance from the pyramid receivers. Ultrasonic waves transmitted from the transducer were converted into electrical field by the pyramid receivers. Output voltages under varying load conditions were recorded using an oscilloscope to confirm the mechanical-to-electrical energy conversion efficiency.
For biological evaluation, the pyramid receivers were sterilized through sequential immersion in 70% ethanol supplemented with antibiotics, followed by rinsing with Dulbecco’s Phosphate-Buffered Saline (DPBS) and air drying. U251 glioblastoma cells were seeded at a density of 2 × 10⁴ cells per well in 24-well plates and exposed to wireless TTF for 60 minutes. 48 hours post-exposure, cell viability was assessed using the CCK-8 colorimetric assay.

Results, Conclusions, and Discussions:: The pyramid ultrasonic receiver exhibited robust wireless power transfer performance under ultrasonic excitation. As shown in Fig. 2a, a single unit generated ~10 V open-circuit voltage at 670 kHz, with the sinusoidal waveform confirming efficient ultrasonic energy conversion. Output voltage and current varied with external load resistance (Fig. 2b), peaking at ~400 Ω with 132.08 mW/cm³ maximum power, consistent with impedance-matching principles. Polar plots (Figs. 2c and 2d) revealed angular dependence for series and parallel configurations. Maximum output (~7 V) occurred when ultrasonic waves were aligned with the receivers, demonstrating rotational symmetry and omnidirectional powering.
The feasibility of wireless ultrasonically powered TTF using a pyramid ultrasonic receiver was demonstrated in vitro (Fig. 3a). The generated localized electric fields showed significant reduction in U251 glioblastoma cells; CCK-8 assay results showed viability to 55.54% in the TTF group, compared to sham (90.47%) and control (100%) (Fig. 3b). Bright-field images also revealed TTF-induced apoptotic morphology, including cell fragmentation and morphological change (Fig. 3c).
These findings validate wireless ultrasonic-powered TTF as a promising approach for disrupting glioblastoma proliferation, with potential for treating deep-seated tumors. Building on our findings, future studies will optimize parameters and validate in vivo.

Acknowledgements and/or References (Optional):: This work was supported by the National Science Foundation (NSF) CAREER (No. ECCS-2245090) (Kim) and FL DOH (MOADB)