Metastable interface biomimetic synthesis of a smart nanosystem for enhanced starvation/gas therapy

Glucose oxidase (GOx)-mediated starvation therapy holds great promise in cancer treatment. However, the worse hypoxia conditions result into low therapeutic efficiency, and undegradability of carriers poses potential threats to living bodies. To address this, herein a bioinspired MnO₂ nanosystem with controllable surface was developed for highly efficient starvation/gas synergistic enhanced therapy. Biomimetic design and further surface modification unprecedentedly endowed the nanosystem with ultrahigh loading capacity for GOx and l-Arginine (l-Arg) and special selectivity toward cancer cells. Especially, the dissipative O₂ during starvation therapy was well replenished by a positive cycle formed by the nanosystem, which continuously reproduced O₂ and accelerated glucose consumption. The abundant H₂O₂ was further used to oxidize l-Arg into nitric oxide to realize gas therapy. In vitro and in vivo testing confirmed that this new treatment effectively blocked the nutrition and energy sources of cells to obtain excellent therapeutic effect. We reported the first experimental item of this nanosystem for inhibiting cancer cell migration. Considering the novel design concept with facile biomimetic methods, effective co-loading of endogenous substances, and good anti-tumor and anti-migration effects, this work provided new theoretical and experimental basis for starvation therapy and inspired people to design more delicate platform for cancer treatment.