Cavitation behaviors of genetically engineered bacterial protein nanoparticles induced by pulsed ultrasound

Genetically engineered bacterial protein nanoparticles (GVs-E.coli) enhance the therapeutic efficacy of high-intensity focused ultrasound (HIFU) by virtue of their intrinsic tumor tropism, favorable biosafety profile, and inherent cavitation activity. However, the cavitation behavior of GVs-E.coli has not been systematically characterized, and the underlying regulatory mechanisms remain poorly elucidated presenting a critical knowledge gap that limits their optimal theranostic application. Herein, we investigated the cavitation behaviors of GVs-E.coli within a wall-free flow channel embedded in tissue-mimicking agarose phantoms using a customized ultrasound platform. Passive cavitation detection (PCD) was performed under varying peak negative pressures (PNPs) and bacterial concentrations, with acoustic emissions analyzed in both time and frequency domains. Our results revealed that the stable cavitation (SC) threshold of GVs-E.coli was 1.6 MPa and the inertial cavitation (IC) threshold was 2.2 MPa. Cavitation dose was positively correlated with PNP, yet harmonics and sub-harmonics exhibited distinct growth patterns.A critical concentration threshold of OD₆₀₀ (optical density at 600 nm) = 1.0 was identified for robust cavitation activity. These findings lay the groundwork for optimizing GVs-E.coli-mediated ultrasound therapies and accelerate their clinical translation as next-generation sonosensitizers.