Barium titanate piezoelectric nanoparticles induce M1 polarization in mouse macrophages via ultrasound in vitro

Macrophages are critical for the maintenance of immune system homeostasis. They differentiate into distinct functional populations, from pro-to anti-inflammatory phenotype, exhibiting remarkable biological plasticity and responding to both chemical and physical cues to achieve these phenotypes. Controlling macrophage cell phenotypes in vivo, with temporal and spatial control, could have significant impact on a wide range of human diseases and ailments associated with inflammation, which range from rheumatoid arthritis and Alzheimers to cancer tumorigenesis. Piezoelectrics, materials in which pressure causes a voltage and vice versa, represent a potential platform for non-invasive and remote modulation of cells and tissues and, in particular, control of immune cell activation. Here, it is demonstrated that RAW264.7 mouse macrophage cells that have taken up piezoelectric nanoparticles (pzNPs) specifically adopt an M1 cellular phenotype and requisite calcium ion influx upon ultrasound stimulation. One can further identify which cells have taken up pzNPs and which cells adopt an M1 polarization in mixed populations of pzNP-loaded and -unloaded cells. The overall goal is to leverage this novel cellular assay to help improve understanding of how biological cells respond to bioelectric stimulation.