Erythrocyte Membrane Cloaked Metal–Organic Framework Nanoparticle as Biomimetic Nanoreactor for Starvation-Activated Colon Cancer Therapy

Abstract

Shutting down glucose supply by glucose oxidase (GOx) to starve tumors has been considered to be an attractive strategy in cancerous starvation therapy. Nevertheless, the in vivo applications of GOx-based starvation therapy are severely restricted by the poor GOx delivery efficiency and the self-limiting therapeutic effect. Herein, a biomimetic nanoreactor has been fabricated for starvation-activated cancer therapy by encapsulating GOx and prodrug tirapazamine (TPZ) in an erythrocyte membrane cloaked metal–organic framework (MOF) nanoparticle (TGZ@eM). The fabricated TGZ@eM nanoreactor can assist the delivery of GOx to tumor cells and then exhaust endogenous glucose and O2 to starve tumors efficiently. Importantly, the resulting tumor hypoxia by GOx-based starvation therapy further initiates the activation of TPZ, which is released from the nanoreactor in the acid lyso/endosome environment, for enhanced colon cancer therapy. More importantly, by integrating the biomimetic surface modification, the immunity-escaping and prolonged blood circulation characteristics endow our nanoreactor dramatically improved cancer targeting ability. The in vitro and in vivo outcomes indicate our biomimetic nanoreactor exhibits a strong synergistic cascade effect for colon cancer therapy in an accurate and facile manner.