Protein Fibril-Based Intracellular Sono-Piezocatalysis via Nanoparticle-Enhanced Piezoelectricity

Piezoelectricity of protein fibrils have unique potential for mechanical stress-assisted cell therapy. However, a stronger piezoelectric property requires micron-length fibrils that lower their colloidal property with limited cellular targeting. Here, we report colloidal lysozyme fibrils with moderate piezoelectric property (29 pm/V) suitable for intracellular piezocatalysis under mechanical stress followed by oxidative cell death. We have designed nanoparticle-conjugated lysozyme fibrils of ∼300-400 nm average length and 20 nm average diameter that enhance the piezoelectric property of fibrils by 2 times and therapeutic potential up to 10 times. The colloidal composite is functionalized with affinity molecules for selective cell targeting/labeling and then exposed with ultrasound for piezocatalytic generation of reactive oxygen species inside the cell, which results in cellular apoptosis. The observed results suggest that the piezoelectric property of protein fibrils has unique therapeutic potential that is yet to be explored.