Marshall Laboratory of Biomedical Engineering, International Cancer Center, Laboratory of Evolutionary Theranostics (LET), School of Biomedical Engineering, Shenzhen University Health Science Center, Shenzhen, 518060, China.
Angew Chem Int Ed Engl. 2022 Oct 17;61(42):e202204584. doi: 10.1002/anie.202204584. Epub 2022 Sep 12.
Glucose and lactate play important roles for tumor growth. How to simultaneously deprive tumors of glucose and lactate is a big challenge. We have developed a cascade catalytic system (denoted as FPGLC) based on fluorinated polymer (FP) with co-loading of glucose oxidase (GOx), lactate oxidase (LOx), and catalase (CAT). GOx and LOx deprive glucose and lactate, respectively, resulting in abundant hydrogen peroxide (H O ) generation. Meanwhile, CAT catalyzes H O into O , which not only promotes catalytic reactions of GOx and LOx for consuming more glucose and lactate, but also alleviates tumor hypoxia. Benefiting from the excellent cross-membrane and transmucosal penetration capacities of FP, FPGLC rapidly accumulated in tumors and subsequently mediated enhanced cascade catalytic therapy under the guidance of photoacoustic imaging. These results demonstrate that the dual depletion of glucose and lactate with O supply is a promising strategy for efficient antitumor starvation therapy.
葡萄糖和乳酸在肿瘤生长中起着重要作用。如何同时剥夺肿瘤的葡萄糖和乳酸是一个巨大的挑战。我们开发了一种基于氟化聚合物（FP）的级联催化系统（表示为 FPGLC），该系统共载有葡萄糖氧化酶（GOx）、乳酸氧化酶（LOx）和过氧化氢酶（CAT）。GOx 和 LOx 分别剥夺葡萄糖和乳酸，导致大量过氧化氢（H2O2）的生成。同时，CAT 将 H2O2 催化为 O2，这不仅促进了 GOx 和 LOx 的催化反应以消耗更多的葡萄糖和乳酸，还缓解了肿瘤缺氧。得益于 FP 优异的跨膜和跨黏膜穿透能力，FPGLC 迅速在肿瘤中积累，并在光声成像的指导下介导增强的级联催化治疗。这些结果表明，供应 O2 以双重消耗葡萄糖和乳酸是一种很有前途的高效抗肿瘤饥饿治疗策略。
