Nanoscale CaH2 materials for synergistic hydrogen-immune cancer therapy

Herein, we prepared CaH2 nanoparticles through liquid-phase exfoliation and first applied them as an antitumor therapeutic agent. Being dispersed in low-molecular-weight polyethylene glycol (PEG) and injected into the tumor, nano-CaH2 would react with water to generate abundant hydrogen gas (H-2), calcium ions (Ca2+), and hydroxyl ions (OH-), enabling hydrogen therapy, tumor calcification, and neutralization of acidic tumor microenvironment (TME), respectively. The injectable nano-CaH2 dispersion could lead to significant tumor growth inhibition. In addition, the local nano-CaH2-induced tumor cell apoptosis and TME modulation would activate the immune system and promote tumor infiltration of immune cells, which, working together with immune checkpoint blockade, could elicit robust immune responses to inhibit abscopal distant tumors without direct nano-CaH2 injection. Furthermore, nano-CaH2 could be dispersed in lipiodol to obtain CaH2-lipiodol dispersion for interventional transarterial embolization (TAE) therapy, and they showed obviously improved TAE therapeutic outcome on orthotopic rabbit liver cancer model compared with lipiodol alone.

Automated summary

In this study, CaH2 nanoparticles were prepared through liquid-phase exfoliation and used as an antitumor therapeutic agent. When injected into the tumor, the nano-CaH2 reacts with water to produce hydrogen gas, calcium ions, and hydroxyl ions, which enable hydrogen therapy, tumor calcification, and neutralization of the acidic tumor microenvironment. The results showed that the injectable nano-CaH2 dispersion significantly inhibited tumor growth and activated the immune system to promote immune cell infiltration into the tumor, resulting in robust immune responses to inhibit distant tumors. Furthermore, nano-CaH2 dispersed in lipiodol showed improved therapeutic outcomes in interventional transarterial embolization therapy compared to lipiodol alone in a liver cancer model.