Biocatalytic Depletion of Tumorigenic Energy Sources Driven by Cascade Reactions for Efficient Antitumor Therapy

Abstract

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 (H₂ O₂ ) generation. Meanwhile, CAT catalyzes H₂ O₂ into O₂ , 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 O₂ supply is a promising strategy for efficient antitumor starvation therapy.

Keywords: Antitumor Therapy; Cascade Catalytic Reactions; Fluorinated Polymers; Glucose Depletion; Lactate Depletion.