双活性纳米酶启动串联催化以双重增强 ATP 耗竭抗肿瘤治疗

Nanozymes can regulate metabolism to achieve precise anti-tumor therapy.

However, the application of nanozymes with single catalytic properties is limited by complex tumor microenvironment (TME).

Herein, we report a rarely discovered nanozyme ruthenium (Ru), which has double catalytic activity of glucose-oxidase-like (GOx-like) activity and peroxidase-like (POD-like) activity.

Importantly, the GOx-like activity of Ru was proposed for the first time, which can catalyze glucose and O 2 to product H 2 O 2 . And then, Ru nanozyme can connect the tandem catalysis to enhance various tumor therapy. Firstly, the atovaquone (ATO) and Ru NPs were covered with a hybrid membrane of tumor cells and liposomes to obtain Ru@ATO-Lip/M with homologous targeting.

Due to the enhanced permeability and retention (EPR) effect and the tumor targeting, the Ru@ATO-Lip/M NPs could be efficiently delivered to tumor and taken up by tumor cells. Subsequently, the acidic environment of tumor activated Ru to catalyze H 2 O 2 producing OH (Fenton-like reaction). Meanwhile, newly discovered ability of Ru catalyzed glucose and O 2 to produce gluconic acid and H 2 O 2 , which provided sufficient substrates (H 2 O 2 ) for continuously generating more OH.

Therefore, Ru nanozyme aggravated the starvation and chemodynamic therapy (CDT).

Further, ATO improved the hypoxia of the tumor microenvironment, achieving steadily synergistic anti-tumor effect.

This study verified the glucose oxidase-like properties of Ru NPs for the first time, and the strategy enhanced the synergistic anti-tumor effects by CDT and starvation therapy, which provided a basis for further exploration of Ru nanozyme activity and application on antitumor.