Cancer Cell Membrane-Biomimetic Nanoplatform for Enhanced Sonodynamic Therapy on Breast Cancer via Autophagy Regulation Strategy

Autophagy was considered as a double-edged sword that might cooperate, aggravate, or antagonize apoptosis. We found that the sonodynamic therapy (SDT) in low dosage induced autophagy and might function as a survival pathway for breast cancer and exhibit resistance to SDT-mediated apoptosis. In this sense, it was highly desired to enhance SDT via autophagy regulation strategy. Herein, we reported a biomimetic nanoplatform based on hollow mesoporous titanium dioxide nanoparticles (HMTNPs) by autophagy inhibitor (hydroxychloroquine sulphate, HCQ) loading and cancer cell membrane (CCM) coating. Owing to the biomimetic surface functionalization, the CCM-HMTNPs/HCQ could escape from macrophage phagocytosis, actively recognize and home in on the tumor by homologous targeting ability. Afterward, the released HCQ in response to the ultrasound stimulus was capable of blocking the autophagic flux and cutting off the nutrients supply derived from the damaged organelles, which was anticipated to abrogate the cells' resistance to SDT. Meanwhile, the vessel normalization effect of HCQ alleviated the tumor hypoxia, which was bound to enhance the oxygen-dependent HMTNPs-mediated SDT treatment. Based on the above findings, it was undoubtedly logical that CCM-HMTNPs/HCQ would sensitize breast cancer cells to SDT via autophagy regulation strategy, which held a great promise in cancer treatment.