Surface Functionalized Biomimetic Bioreactors Enable the Targeted Starvation-chemotherapy to Glioma

Altering the glucose supply and the metabolic pathways would be an intriguing strategy in starvation therapy toward cancers. Nevertheless, starvation therapy alone could be inadequate to eliminate tumor cells completely. Herein, a multifunctional bioreactor was fabricated for synergistic starvation-chemotherapy through embedding glucose oxidase (GOx) and doxorubicin (DOX) in the tumor targeting ligands (RGD) modified red blood cell membrane camouflaged metal-organic framework (MOF) nanoparticle (denoted as RGD-mGZD). Owing to the remarkable biointerfacing property, the designed RGD-mGZD could not only possess enhanced blood retention time inherited from red blood cells, but also preferentially target the tumor site after the modification with RGD peptide. Once the bioreactor reached the desired region, GOx promptly consumed the intratumoral glucose and oxygen to starve cancer cells for robust starvation therapy. More importantly, the aggravated acidic microenvironment at the tumor region was found to induce the decomposition of the MOF structure, thus triggering the release of DOX for reinforced chemotherapy. This bioreactor would further prompt the development of synergistic patterns toward cancer treatment in a spatiotemporally controlled manner.