Sonochemotherapy is a promising strategy for inhibiting
tumor growth. However, achieving highly targeted and effective sonochemotherapy is still an enormous challenge. In this study, a novel chemotherapeutic-carrying nanocomposite (HPCID) was developed, which can effectively target metastatic
cancer cells and provide an enhanced
therapeutic effect. In detail, HPCID was composed of
hyaluronic acid (HA), carboxyl-terminated
PAMAM dendrimer,
fluorochrome indocyanine green (ICG), and
doxorubicin hydrochloride (Dox). The efficacy of this drug delivery system (DDS) in sonochemotherapy was assessed on the CD44-overexpressing metastatic
breast cancer cell line 4T1 both in vitro and in vivo. The HA modification significantly improved the cellular internalization of HPCID, and the degradation of the HA shell by
hyaluronidase that is abundant in the 4T1 cells resulted in
enzyme-responsive drug release. Under ultrasound (US) stimulation, HPCID produced a high amount of reactive
oxidant species (ROS), which induced significant cell apoptosis when combined with
chemotherapy. In addition, the administration of HPCID in 4T1 xenograft-bearing mice combined with ultrasonic exposure significantly inhibited
tumor growth and pulmonary
metastasis, with no systemic toxicity. Taken together, the proposed HPCID-mediated sonodynamic
therapy (SDT) is a novel strategy against
breast cancer progression and
metastasis.