Ultrasound-Responsive Oxygen-Carrying Pollen for Enhancing Chemo-Sonodynamic Therapy of Breast Cancer

The tumor-suppressing efficacy of either chemotherapeutics or gaseous drugs has been confirmed in treating the triple negative breast cancer (TNBC), while the efficacy of single treatment is usually dissatisfactory. Herein, a novel ultrasound responsive natural pollen delivery system is presented to simultaneously load chemotherapeutics and gaseous drugs for synergistic treatment of TNBC. The hollow structure of pollen grains carries oxygen-enriched perfluorocarbon (PFC), and the porous spinous process structure adsorbs the chemotherapeutic drug doxorubicin (DOX) (PO/D-PGs). Ultrasound can trigger the oxygen release from PFC and excite DOX, which is not only a chemotherapeutic but also a sonosensitizer, to realize chemo-sonodynamic therapy. The PO/D-PGs are demonstrated to effectively enhance oxygen concentration and increase the production of reactive oxygen species in the presence of low-intensity ultrasound, synergistically enhancing the tumor killing ability. Thus, the synergistic therapy based on ultrasound-facilitated PO/D-PGs significantly enhances the antitumor effect in the mouse TNBC model. It is believed that the proposed natural pollen cross-state microcarrier can be used as an effective strategy to enhance chemo-sonodynamic therapy for TNBC.