A core–shell liquid metal-Cu nanoparticle with glutathione consumption via an in situ replacement strategy for tumor combination treatment of chemodynamic, microwave dynamic and microwave thermal therapy

Abstract

The presence of high content glutathione (GSH) provides an effective “protective shield” for tumor cells, which undoubtedly is a huge impediment to reactive oxygen species (ROS)-based treatment. Fortunately, divalent copper (Cu²⁺) can not only consume GSH, destroying the protection mechanism of GSH, but also can be reduced to Cu⁺ with excellent Fenton-like reaction activity. Hence, capitalizing on the properties of liquid metals, we introduced Cu with three different valances via an in situ replacement reaction. A stable core–shell liquid-metal based “Cu storage pool” was obtained. It can effectively deplete GSH within the cells, and simultaneously produce ·OH through a Fenton-like reaction, further improving the effect of chemodynamic therapy (CDT). Under microwave irradiation, it is also capable of producing a large amount of ROS to promote tumor treatment. In addition, the loading of ionic liquid endows LZC@IL nanoparticles with certain microwave heating performance, which is able to augment microwave thermal therapy (MWTT). With the combination of CDT, microwave dynamic therapy (MDT) and MWTT, LZC@IL has an excellent effect on tumor elimination. This work offers a new idea for the application of liquid metals and the combined treatment of tumors, which has potential application value.