Magnetic-Acoustic Microbubble Microrobot for Targeted Mechanical Stimulation of Cancer Cells

Abstract

Mechanical stimulation has recently been shown as a promising approach to induce targeted cancer cell death. With precise field control, magnetic microrobots were navigated to the tumor site for delivering mechanical stimulation as a new treatment approach. However, most magnetic microrobots suffer from low force output when generating mechanical stimulation. Acoustic microrobots, with a microbubble as their simplest form, generate strong mechanical stimulation yet lack precise position control. In this paper, leveraging the force output of the acoustic field and precision of magnetic field control, we present a magnetic acoustic microbubble microrobot (MAM) that integrates magnetic navigation and acoustic stimulation. MAMs were fabricated with DSPC/PEG lipid shells and iron-oxide nanoparticles (IONPs) using a flow-focusing microfluidic method. The size of the fabricated monodispersed MAMs is approximately 10 μm. The fabricated MAMs were navigated by a quadrupole magnetic tweezer system, with a maximum field gradient of 2–3 T/m, and controlled to oscillate to generate mechanical stimulation under an acoustic transducer at 1 MHz. As a proof-of-concept, we applied MAM acoustic treatment to breast cancers (MDA-MB-231) and showed that MAM acoustic treatment led to reduced cell viability compared to the control group and the acoustic-only group. Considering all the components for MAM fabrication are FDA-approved materials, MAM holds promise for clinical translation in tumor mechanical stimulations.