Method and medical devices for generating and stabilizing micro- or nano-bubbles, and systems and methods for therapeutic applications using the bubbles, are provided. The micro-bubbles may be used to enhance therapeutic benefits such as ultrasound-guided precision drug delivery and real-time verification, acoustic activation of large tumor masses, enhanced acoustic activation through longer retention of therapeutic agents at the point of interest, enhancement of high intensity focused ultrasound treatments, light activation of photodynamic drugs at a depth within a patient using extracorporeal light sources, probes, or sonoluminescence, and initiation of time reversal acoustics focused ultrasound to permit highly localized treatment.