Sono-dynamic synergy of DOX-MBs achieves real-time imaging-guided drug delivery for breast cancer.

Doxorubicin (DOX) is a widely used first-line chemotherapeutic drug with potent anti-tumor activity, yet severe off-target cardiotoxicity and hepatotoxicity severely restrict its clinical application. This study aimed to construct an ultrasound-responsive PLGA microbubble delivery system to realize tumor-specific controlled DOX release under low-intensity focused ultrasound (US), integrate real-time ultrasonic tumor imaging, and simultaneously reduce systemic side effects of free DOX. DOX-loaded PLGA microbubbles (DOX-MBs) were fabricated and evaluated for ultrasound contrast enhancement and US-triggered intracellular DOX release. In vitro and in vivo experiments were performed to evaluate tumor cell apoptosis induction, anti-metastatic capacity, as well as cardiac and hepatic toxic side effects of this theranostic platform. The DOX-MB system enabled real-time ultrasound visualization of tumor lesions. US exposure disrupted the microbubbles and promoted intracellular DOX release. Compared with free DOX, this platform significantly elevated tumor cell apoptosis, suppressed tumor distant metastasis, and effectively alleviated DOX-induced cardiotoxicity and hepatotoxicity in vivo. The developed US-activated DOX-loaded PLGA microbubbles integrate diagnostic ultrasound imaging and tumor-targeted chemotherapy with reduced organ toxicity. This work provides a facile and novel design strategy for imaging-guided, ultrasound-triggered tumor theranostic microplatforms.