Biomimetic Metal-Chalcogenide Agents Enable Synergistic Cancer Therapy via Microwave Thermal-Dynamic Therapy and Immune Cell Activation.

Abstract

Microwave thermal dynamic therapy (MTDT), which combines thermal effects and reactive oxygen species (ROS) by microwave activation, seems to be a promising anticancer therapeutic method. A multifunctional agent for achieving synergistic localized cancer treatment is the key to exploit the strategy to inhibit tumor cell recurrence and metastasis. In the study, a ZIF-67 based theranostic agent loaded with metal-chalcogenide open framework 3 (MCOF3) and heat shock protein 70 (HSP70) as the inner component was studied, coupled with targeting cancer cell membrane (TCM) as the biomimetic outer shell. We found that metal ions in MCOF3 enabled the composite agents to show peroxide-like activity to produce •OH and destroy cancer cells. And then, the microwave (MW) thermal sensitizer of ZIF-67 was used to specifically convert the MW energy into thermal energy and selectively heat the tumor via the cell's targeting. Additionally, the effect of continuous MW thermal therapy has been shown to promote the expression of HSP70, and further activate the effector of CD4 T cell and CD8α T cell. As such, the agents effectively inhibit the tumor cell growth under MW irradiation in vitro and in vivo due to the synergistic effects of MTDT and immune cell activation. The study provides an emerging strategy to ablation cancer effectively.