Tumor Microenvironment-Responsive Dual-Enzymatic Flasklike Nanobots for Enhanced Chemotherapy

We report a glucose oxidase/catalase-driven, tumor cell membrane-camouflaged flasklike pentosan nanobot (GC-M@FPNbot) to achieve targeted drug delivery in response to the characteristic concentration gradients within the tumor microenvironment (TME), thereby enhancing the efficacy of tumor chemotherapy. The doxorubicin-loaded GC-M@FPNbots, propelled by an enzymatic cascade reaction, exhibit a pronounced chemotactic behavior along proton and/or hydrogen peroxide concentration gradients. This chemotactic propulsion enables the nanobots to efficiently penetrate the extracellular matrix barrier and deeply infiltrate 3D multicellular tumor spheroids, thereby significantly improving tumor tissue permeation. In a murine tumor model, the directional motility of these nanobots enhances their tumor targeting delivery efficiency, achieving a 5.7-fold increase compared to passive flasklike pentosan particles. Furthermore, the GC-M@FPNbots exhibit an 80.8% tumor growth inhibition rate over 16 days, surpassing the 47.6% inhibition achieved by conventional chemotherapeutic agents. Such dual-enzymatic nanobots capable of TME-responsive directional movement mimicking the positively chemotactic behavior of immune cells hold the potential for personalized therapeutic strategies.