文献：

Glucose & Oxygen Exhausting Liposomes for Combined Cancer Starvation and Hypoxia-Activated Therapy

文献链接：

https://www.sciencedirect.com/science/article/abs/pii/S014296121830084X

作者：

Rui Zhang, Liangzhu Feng, Ziliang Dong, Li Wang, Chao Liang, Jiawen Chen, Qingxi Ma, Rui Zhang, Qian Chen, Yucai Wang‡ , Zhuang Liu

相关产品：

胆固醇、DSPE-mPEG5k

原文摘要：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 H2O2. Such liposome-GOx after intravenous injection with effective tumor retention is able to exhaust glucose and oxygen within the tumor, producing cytotoxic H2O2 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.

脂质体是一种纳米药物载体，具有生物相容性、药代动力学特性和多种载药能力。饥饿疗法通过切断tumor的能量供应来减缓tumor的生长，葡萄糖氧化酶（GOx）被装载到隐形脂质体中，并作为葡萄糖和氧消除剂，触发葡萄糖和氧转化为葡萄糖酸和过氧化氢。这种脂质体-gox在静脉注射后，能有效保留tumor，能够排出tumor内的葡萄糖和氧气，产生细胞有害性过氧化氢，增强缺氧，通过无创体内光声成像可见。通过进一步联合使用装载二盐酸巴诺蒽醌（AQ4N）的隐形脂质体进行应用，在4T1tumor小鼠模型中实现了协同增强的tumor生长抑制作用。通过结合饥饿疗法和缺氧激活疗法，设计胆固醇和DSPE-mPEG5k参与制备纳米载体共同传递酶和前药。过程如下：

脂质体制备

为制备脂质体-gox和脂质体-aq4n，将DPPC、胆固醇和DSPE-mPEG5k的脂质混合物以一定摩尔比溶解成氯仿。然后在真空下干燥脂质溶液。然后，将获得的脂质用AQ4N或GOx溶液水合，搅拌，然后通过聚碳酸酯过滤器挤压20次。分别使用GS-300高分辨率的acal柱（GE医疗保健）和Sephadex G-100（Sigma）去除多余的GOx和AQ4N。，将GOx酶和小分子缺氧激活前药AQ4N分别封装到聚乙二醇化脂质体中，用于饥饿和缺氧激活的联合Treatment （图a）。经过仔细优化，按照标准的脂质体合成方法，分别用GOx和AQ4N水溶液按照一定比例DPPC、胆固醇和DSPE-mPEG5k混合脂质膜，得到脂质体-AQ4N和脂质体-GOx。

图：脂质体的实验设计与表征方案

结论：基于gox的饥饿Treatment 和基于胆固醇和DSPE-mPEG5k参与制备的纳米载体的aq4n的缺氧激活Treatment 相结合。GOx和AQ4N被封装在长循环的隐形脂质体中后，可以依次传递到具有高tumor归巢效率的tumor中。这种脂质体-gox可以特异性地阻断tumor葡萄糖供应，排出tumor氧以增强缺氧，并在tumor内产生有害的过氧化氢。同时，脂质体-aq4n一旦进入缺氧增强的tumor，就会被进一步激活，从而达到较强的协同抗tumor作用。