Dual Enzyme‐Encapsulated Materials for Biological Cascade Chemistry and Synergistic Tumor Starvation

Abstract

AbstractFramework and polymeric nanoreactors (NRs) have distinct advantages in improving chemical reaction efficiency in the tumor microenvironment (TME). Nanoreactor‐loaded oxidoreductase enzyme is activated by tumor acidity to produce H2O2 by increasing tumor oxidative stress. High levels of H2O2 induce self‐destruction of the vesicles by releasing quinone methide to deplete glutathione and suppress the antioxidant potential of cancer cells. Therefore, the synergistic effect of the enzyme‐loaded nanoreactors results in efficient tumor ablation via suppressing cancer‐cell metabolism. The main driving force would be to take advantage of the distinct metabolic properties of cancer cells along with the high peroxidase‐like activity of metalloenzyme/metalloprotein. A cascade strategy of dual enzymes such as glucose oxidase (GOx) and nitroreductase (NTR) wherein the former acts as an O2‐consuming agent such as overexpression of NTR and further amplified NTR‐catalyzed release for antitumor therapy. The design of cascade bioreductive hypoxia‐responsive drug delivery via GOx regulates NTR upregulation and NTR‐responsive nanoparticles. Herein, we discuss tumor hypoxia, reactive oxygen species (ROS) formation, and the effectiveness of these therapies. Nanoclusters in cascaded enzymes along with chemo‐radiotherapy with synergistic therapy are illustrated. Finally, we outline the role of the nanoreactor strategy of cascading enzymes along with self‐synergistic tumor therapy.