Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Institute of Functional Nano & Soft Materials (FUNSOM), Jiangsu Key Laboratory for Carbon-Based Functional Materials & Devices, Soochow University, Suzhou, 215123, China.
Biomaterials. 2018 Apr;162:123-131. doi: 10.1016/j.biomaterials.2018.02.004. Epub 2018 Feb 3.
Starvation therapy to slow down the tumor growth by cutting off its energy supply has been proposed to be an alternative therapeutic strategy for cancer treatment. Herein, glucose oxidase (GOx) is loaded into stealth liposomes and act as the glucose and oxygen elimination agent to trigger the conversion of glucose and oxygen into gluconic acid and HO. Such liposome-GOx after intravenous injection with effective tumor retention is able to exhaust glucose and oxygen within the tumor, producing cytotoxic HO and enhancing hypoxia, as vividly visualized by non-invasive in vivo photoacoustic imaging. By further combination treatment with stealth liposomes loaded with banoxantrone dihydrochloride (AQ4N), a hypoxia-activated pro-drug, a synergistically enhanced tumor growth inhibition effect is achieved in the mouse model of 4T1 tumor. Hence, by combining starvation therapy and hypoxia-activated therapy tactfully utilizing liposomal nanocarriers to co-deliver both enzymes and prodrugs, an innovative strategy is presented in this study for effective cancer treatment.
通过切断肿瘤能量供应来减缓肿瘤生长的饥饿疗法被提议作为癌症治疗的一种替代治疗策略。在此，葡萄糖氧化酶（GOx）被装载到隐形脂质体中，充当葡萄糖和氧气清除剂，以触发葡萄糖和氧气转化为葡萄糖酸和 HO。这种脂质体-GOx 经静脉注射后具有有效的肿瘤保留能力，能够耗尽肿瘤内的葡萄糖和氧气，产生细胞毒性 HO 并增强缺氧，如通过非侵入性体内光声成像生动地可视化。通过进一步与负载盐酸氨柔比星（AQ4N）的隐形脂质体联合治疗，一种缺氧激活的前药，在 4T1 肿瘤的小鼠模型中实现了协同增强的肿瘤生长抑制效果。因此，通过巧妙地结合饥饿疗法和缺氧激活疗法，利用脂质体纳米载体共递送酶和前药，本研究提出了一种用于有效癌症治疗的创新策略。
