Tumor Microenvironment Triggered the In Situ Synthesis of an Excellent Sonosensitizer in Tumor for Sonodynamic Therapy

An ultrasound-triggered sonodynamic therapy has shown great promise for cancer therapy. However, its clinical applications are very limited because the traditional sonosensitizers tend to suffer from very poor efficiency combined with low retention in cancer cells and low tumor selectivity. Therefore, sonosensitizers with higher effectivity, higher tumor cell retention, and higher tumor cell specificity are highly required. Herein, we constructed a Ti2C(OH)(X) nanosheet, which was a poor sonosensitizer but had a long circulation in the blood system. However, it was very interesting to find that the tumor microenvironment could in situ turn Ti2C(OH)(X) nanosheet into a novel and excellent sonosensitizer with a nanofiber structure in tumors, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. Moreover, the nanofiber structure made it very difficult to get out of cancer cells, highly enhancing the retention of the sonosensitizer in the tumor, thereby enabling it to effectively and selectively kill cancer cells in vivo. Our findings demonstrate that the strategy of the tumor microenvironment triggering the in situ synthesis of an effective sonosensitizer in tumor provided a promising means to simultaneously increase the efficiency, sonosensitizer retention in cancer cells, and cancer selectivity, thereby effectively killing cancer cells but causing little damage to healthy tissues via the sonodynamic therapy.

Automated summary

Ultrasound-triggered sonodynamic therapy has shown great potential for cancer treatment. However, traditional sonosensitizers have low efficiency, short retention time in cancer cells, and poor tumor selectivity. Therefore, there is a strong need for sonosensitizers with higher efficacy, longer retention in tumor cells, and greater specificity. In this study, we developed a Ti2C(OH)(X) nanosheet, which was transformed into a novel nanofiber structure sonosensitizer in the tumor microenvironment, exhibiting excellent ability to generate reactive oxygen species (ROS) under ultrasound. This nanofiber structure enabled high retention of the sonosensitizer in the tumor and effectively and selectively killed cancer cells.