Hollow Co-CeO 2@PEG nanospheres: Ultrasound enhanced cascade-nanozyme for synergetic anticancer

The limited H2O2 level in tumor microenvironment (TEM) constrains the effect of chemodynamic therapy (CDT). Herein, Co-CeO2@PEG hollow nanospheres are synthesized for two strategies of H2O2-supply. By varying hy-drothermal times, hollow Co-CeO2 nanospheres (similar to 55 nm) are prepared derived from Ostwald ripening. Under ultrasound (US) irradiation, reactive oxygen species (ROS) are generated due to cavitation effect. ESR and capturing experiments reveal the US energy transfer (1O2) and US-generated electrons/dissolved O-2 (H2O2) to determine ROS production. The doping of Co increases oxygen vacancy, which is in favor of O-2 adsorption and ROS generation. Both density functional theory (DFT) calculation and experimental measurement reveal the decreased band gap of Co-CeO2. The emerging new energy band improves the separation/transfer of electron -hole and ROS production. Besides, hollow structure is significant to introduce extra cavitation nucleus, pro-moting cavitation effect and ROS generation. Furthermore, Co-CeO2@PEG nanospheres reveal glucose oxidase (GOx) activity, which not only can consume endogenous glucose to introduce starvation therapy but also to produce H2O2. The above two ways can realize intracellular H2O2 replenishment. In addition, Co-CeO2@PEG also show mimic peroxidase (POD) and catalase (CAT) behavior to introduce CDT and O-2-supplementation. In comparison with pure CeO2@PEG, the greater nanozyme activity of Co-CeO2@PEG is ascribed to the lower resistance of charge transfer that is further testified by DFT and electrochemical analysis. Synergetic CDT/ starvation/sonodynamic therapy (SDT) reveals noteworthy anticancer efficiency and also arouses immune response for metastasis inhibition.

Automated summary

Co-CeO2@PEG hollow nanospheres are synthesized for H2O2 replenishment in tumor microenvironment (TEM). The Co doping increases oxygen vacancy and promotes ROS generation. The hollow structure introduces extra cavitation nucleus for enhanced cavitation effect and ROS generation. Co-CeO2@PEG also exhibits mimic peroxidase and catalase behavior for chemodynamic therapy (CDT) and O-2 supplementation. Synergetic CDT/starvation/sonodynamic therapy (SDT) shows remarkable anticancer efficiency and immune response for metastasis inhibition.