Ultrasound Triggered Tumor Metabolism Suppressor Induces Tumor Starvation for Enhanced Sonodynamic Immunotherapy of Breast Cancer

Abstract

Kun Qiao,1,* Cheng Luo,2,* Rong Huang,3,4 Jingfeng Xiang,5 You Pan,3,4 Shiyuan Zhang,1 Cong Jiang,1 Shuaijie Ding,6 Huawei Yang,3,4 Yuanxi Huang,1 Shipeng Ning3,4 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Anesthesiology, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, 530000, People’s Republic of China; 4Key Laboratory of Breast Cancer Diagnosis and Treatment Research of Guangxi Department of Education, Nanning, 530000, People’s Republic of China; 5Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 6Department of Gastrointestinal Surgery & Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shipeng Ning; Yuanxi Huang, Email [email protected]; [email protected]: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression.Methods: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation.Results: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth.Conclusion: This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.Keywords: sonodynamic therapy, glycolysis inhibitor, black phosphorus nanosheets, starvation therapy, immune activation

Keywords

• sonodynamic therapy
• glycolysis inhibitor
• black phosphorus nanosheets
• starvation therapy
• immune activation