Dual-frequency excitation enhances targeted delivery of ultrasound microbubbles

Ultrasound radiation force (USRF) is commonly used to facilitate the efficiency of targeted bubble adhesion. Studying the property of adherent bubbles provides opportunities for the further control of targeted drug delivery and release. Previous reports show that USRF provides better targeting efficiency as USRF transmitting frequency close to bubbles´ resonance frequency. However, low-frequency ultrasound suffers from a large sample volume such that USRF cannot be pinpointed to a specified region of interest. In this study, we proposed a high-frequency dual-frequency (DF) excitation with a low-frequency envelope component close to bubbles´ resonance frequency to enhance the bubbles targeting efficiency while retaining a high spatial resolution. The results show that dual-frequency excitation with envelope frequency of 20 MHz (DF-20) and 30 MHz (DF-30) nearing the resonance frequency of submicron bubbles provided targeting enhancement up to 4.6-6.2 folds within 2 minutes. In comparisons to DF-3 and DF-10 excitations, which corresponding envelope frequencies were far from the resonance frequency of submicron bubbles, perform only 2.7-3.3 folds enhancement within 5 minutes.