题目: | A Gas Nanobomb to Promote Drug Penetration and Amplify TACE Therapy for Orthotopic Liver Tumor |
作者: | Minjiang Chen1#, Qinwei Lu1#, Fei Gong2*, Yuqi Yang2, Zifan Pei2, Xuan Huang2, Gaofeng Shu1, Lin Shen1, Peng Yan1, Xiaoju Guo1, Zhuang Liu2, Liang Cheng2*, and Jiansong Ji1* |
单位: | 1Key Laboratory of Imaging Diagnosis and Minimally Invasive Intervention Research, The Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, China 2Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials and Devices, Soochow University, Suzhou 215123, China. |
摘要: | The worsening hypoxia, acidity, immunosuppression, and low drug penetration created by arterial embolization significantly limit the therapeutic efficiency of transarterial chemoembolization (TACE) therapy. To overcome these problems, nanoscale magnesium hydride (MgH2) gas bombs are synthesized and then are co-dispersed with tirapazamine (TPZ) into lipiodol (Lip) to obtain an L-MgH2&TPZ suspension, in which the MgH2 nanobombs efficiently modulate the worsened tumor microenvironment (TME), reversed immunosuppression, promoted drug penetration, and amplified TACE therapy. After being injected into mouse tumors, MgH2 nanobombs react with water to effectively generate OH− to neutralize the acidic TME and reverse immunosuppression; hydrogen (H2) gas bubbles enhance TPZ penetration and achieve hydrogen-based chemotherapy; and Mg2+ synergistically regulates T-cell function, resulting in significant inhibition for tumor growth. Moreover, the immunological effects of H2 and Mg2+-induced antitumor immune responses further inhibit tumor growth and metastasis after combination with an immune checkpoint inhibitor. As demonstrated in the orthotopic rat liver cancer model, transarterial embolization of the L-MgH2&TPZ suspension offers greatly enhanced therapeutic outcomes, and all of tumors are eradicated after 3 weeks of treatment, further confirming that the introduction of the MgH2 nanobombs significantly modulates the acidic/immunosuppressive TME and promotes the penetration of TPZ to improve the efficacy of TACE therapy. |
影响因子: | 26.8 |
分区情况: | 一区 |
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责任编辑:郭佳