Multi-functional EGaIn-ZrO2 composite-spheres with photo-thermal & photodynamic therapies and enhanced radiotherapy and chemodynamic therapy on liver cancer

Abstract

Gallium-based liquid metals (LM) gained wide attention in the biomedical field, with their photo-thermal conversion performance. The composited nano-spheres including soft LM core and zirconium dioxide (ZrO2) shell were prepared, and then they were modified and linked by metronidazole (MN), and targeted RGD peptides, which were called as LM@ZrO2-MN-RGD (named as LZMR). The analysis results of their structure and composition showed that there were the existence of Ga2O3 between LM core and ZrO2 shell, and two irradiation of NIR and X-ray could enhance the value of Ga3+/Ga0 in LZMR. The results of the in vitro and in vivo tests indicated that, LZMR for tumor therapy could not only heating effect under near-infrared (NIR) irradiation (photo-thermal therapy, PTT), but also could produce abundant reactive oxygen species (ROS) to kill Hepa1-6 cells under two irradiation of NIR and X-ray (photodynamic therapy, PDT). Furthermore, LZMR could also clear glutathione (GSH) in vitro and the MN reduced by GSH in tumor field facilitated LZMR higher sensibility on X-Ray and the enhanced radiation therapy (RT). The in vivo inhibition rate of tumor in LZMR group with NIR and X-ray irradiation reached 97%, because the enhanced value of Ga3+/Ga0 under two irradiations could result in the like-Fenton effect in the tumor field to generate ∙OH against cancer cells, achieving the more chemodynamic therapy (CDT) under X-Ray. These results indicated that LZMR was promising to obtain the synergistic effect of PTT, PDT, RT and CDT for enhanced tumor therapy.