Key Laboratory of Biomedical Polymers of Ministry of Education & Department of Chemistry , Wuhan University , Wuhan 430072 , P. R. China.
ACS Appl Mater Interfaces. 2018 May 2;10(17):15030-15039. doi: 10.1021/acsami.8b01818. Epub 2018 Apr 18.
Here, a tumor-targeted MnO motor nanosystem (designed as MG/HA) was constructed by the assembly of glucose oxidase (GOD), manganese dioxide (MnO), and glycoprotein CD44-targeting polymer hyaluronic acid (HA) to elevate cancer-starving therapy efficacy in solid tumor. Upon the specific uptake of MG/HA by CD44 overexpressed cancer cells, GOD catalyzed the oxidation of glucose into gluconic acid and hydrogen peroxide (HO) accompanying the consumption of oxygen (O). Meanwhile, MnO would react with HO and acid to generate O, which is in turn supplied to the glucose-depletion process, running like a loop. As a result, MnO is displayed as a motor to promote the rate of glucose depletion that contributed to the starving therapy. In contrast to G/HA, MG/HA could not only achieve effective glucose consumption to depress cancer progression, but also alleviate hypoxia and reduce the expression of Glut1 to inhibit the metabolism for further restraining the tumor aggressiveness and metastasis. The concept of MnO motor shows a promising prospect to overcome the restriction of the starving therapy.
在这里，构建了一种肿瘤靶向 MnO 运动纳米系统（设计为 MG/HA），通过组装葡萄糖氧化酶（GOD）、二氧化锰（MnO）和糖蛋白 CD44 靶向聚合物透明质酸（HA），以提高实体瘤饥饿治疗的疗效。在 CD44 过表达的癌细胞特异性摄取 MG/HA 后，GOD 催化葡萄糖氧化成葡萄糖酸和过氧化氢（HO），同时消耗氧气（O）。同时，MnO 会与 HO 和酸反应生成 O，O 再次供应给葡萄糖耗竭过程，形成一个循环。结果，MnO 表现为一种促进葡萄糖耗竭的马达，有助于饥饿治疗。与 G/HA 相比，MG/HA 不仅可以有效消耗葡萄糖来抑制癌症进展，还可以减轻缺氧并降低 Glut1 的表达，以抑制代谢，进一步抑制肿瘤侵袭性和转移。MnO 运动的概念显示出克服饥饿治疗限制的广阔前景。
