Homologous Targeting Cascade Nanobioreactor for Autophagy Inhibition Amplified Tumor Catalytic Therapy
Xiaodan Wei, Ningxi Li, Honglin Huang, Geng Yang, Hanxi Zhang, Tingting Li, Xiang Qin, Shun Li, Lulu Cai, Hong Yang, Chunhui Wu, Yiyao Liu
Abstract
Catalytic therapy based on elaborate nanomedicine is emerging as a pioneering modality for tumor-specific treatment. However, its therapeutic efficiency is usually compromised by the self-protective mechanism of cancer cells, such as autophagy. Herein, a homologous targeting cascade nanobioreactor (denoted as CQ/CuZ@M 4T1 -G ) was developed for the autophagy inhibition amplified enzymic-Fenton like catalytic therapy. CQ/CuZ@M 4T1 -G was constructed by wearing Cu 2+ -doped and chloroquine (CQ) loaded zeolitic imidazolate framework with glucose oxidase (GOx) anchored tumor cell membrane. The GOx-driven glycolysis effectively cut off glucose supply for starvation therapy, which also provided abundant H 2 O 2 and decreased pH. Meanwhile, the released Cu 2+ was reduced to Cu + by glutathione and converted the elevated H 2 O 2 into highly toxic ·OH via a Cu + -mediated Fenton-like reaction in the tumor. More importantly, autophagy inhibitor CQ was applied to block downstream autophagic flux and hinder the self-protection pathway. Thus, the tumor succumbed to the severe stress of an enzymatic-Fenton like cascading reaction, yielding a remarkable therapeutic effect as demonstrated by both in vitro and in vivo results. Our study provides a promising regimen mediated by the cascade nanobioreactor for a new type of oncotherapy in the future.