In our study, we developed a novel dual-targeted US imaging agent with C3F8-filled PLGA NBs that attached to VEGFR2 and HER2 and compared the targeting specificity and the resultant US enhancement of dual-targeted NBs with that of single-targeted NBs in VEGFR2-positive and HER2-positive cells and a murine model of breast cancer. Here, ERBB2 is linked to breast cancer.