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 H2O2. 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.