Nonmetallic N/C Nanozyme Performs Continuous Consumption of Glu for Inhibition of Colorectal Cancer Cells.

Colorectal cancer (CRC) is the third leading cause of cancer-related mortality. 5-Fluorouracil (5-FU) is the first choice for treatment of CRC, but it cannot avoid the negative effects from local high glucose (Glu) in tumor. Recently, 5-FU therapy has been combined with other treatment modalities for CRC synergistic therapy. Although these combination therapy strategies are more effective in cancer therapy, the toxicity side effects to the liver and cause metabolic acidosis still exist. Herein, we report an emerging amorphous honeycomb-like nitrogen-doped carbon (N/C) nanozyme with nicotinamide adenine dinucleotide (NADH) oxidase and catalase (CAT) activity and cascade it with natural glucose dehydrogenase (GDH) to realize NAD regeneration and further hyperglycemia management. In this case, by the coupling of N/C nanozyme with natural GDH to form a N/C-GDH system, the electron transfer route can switch from Glu to a common but limited electron receptor, i.e., NAD to ubiquitous large amounts of oxygen, achieving the purpose of sustainable consumption of Glu under NAD circulation and regeneration, and importantly escaping the generation of toxic HO. The combination of the N/C-GDH system and 5-FU on CRC cells was investigated to assess their synergistic bioeffects. Notably, our results showed that the N/C-GDH system and 5-FU in combination significantly suppress the proliferation of human colon cancer cells (HCT-116) by reducing the sugar level and induced apoptosis compared with either material or drug used alone. This work expands the nanozymes in blood Glu management as well as the promising cancer cell inhibition and provides the possibility of nonmetallic nanomaterials in the realization of effective treatment of cancer.