Dual nanoenzymes loaded hollow mesoporous organotantalum nanospheres for chemo-radio sensitization

Chemo-radiotherapy has been extensively used in clinics, displaying substantial advantages in treatment and prognosis. Stimuli-responsive biodegradable nanoagents that can achieve not only delivery and controlled release of chemotherapeutics, but also hypoxia alleviation to enhance chemoradiotherapy therefore has tremendous potential. Herein, glutathione (GSH)-responsive, biodegradable, doxorubicin-carrying hollow mesoporous organotantalum nanospheres modified with Au and Pt dual nanoenzymes (HMOTP@Pt@Au@Dox) were constructed for chemo-radio sensitization. Degradation of HMOTP@Pt@Au@Dox can be self-activated through GSH stimulation and on-demand release packaged Dox owing to the disulfide bond in the hybrid framework of organotantalum nanospheres. Au and Pt nanoenzymes triggered cascade catalytic reactions that could alleviate hypoxia by utilizing beta-D-glucose and H2O2, thereby sensitizing ROS-based chemoradiotherapy with synergistic starving therapy. Given the radiosensitization of high-Z elements (Ta, Pt, Au), nanoenzymes induced cascade catalytic reaction for hypoxia relief, and the depletion of the predominant antioxidant GSH, desirable tumor suppression could be achieved both in vitro and in vivo, indicating that HMOTP@Pt@Au@Dox is a promising nanoagent to boost chemo-radiotherapy.

Automated summary

Chemo-radiotherapy has significant advantages in treatment and prognosis. This study constructed biodegradable nanoagents that can deliver chemotherapeutics and alleviate hypoxia to enhance chemo-radiotherapy. The nanoagents demonstrated self-activation and on-demand release of the chemotherapeutic drug through stimulation by glutathione (GSH). Moreover, the nanoagents triggered cascade catalytic reactions to alleviate hypoxia and enhanced the chemo-radiotherapy effect. The results suggest that these nanoagents have promising potential for boosting chemo-radiotherapy.