Mitochondria-targeted high-load sound-sensitive micelles for sonodynamic therapy to treat triple-negative breast cancer and inhibit metastasis

Breast cancer is the most common cancer among women worldwide, of which 10-20% accounts for triple-negative breast cancer (TNBC). TNBC is more aggressive, lacks an effective treatment target, and has a higher metastasis rate compared to other types of breast cancers. These characteristics result in poor therapeutic and prognostic outcomes in patients with TNBC. Sonodynamic therapy (SDT) is an emerging non-invasive procedure with high-tissue penetration properties to treat cancer. Therefore, we designed a new sonosensitizer, PEG-IR780@Ce6 for SDT, which showed excellent performance in inhibiting cancer cells and in simultaneously suppressing the migration and invasion of cancer cells. In vitro and in vivo experiments showed that PEG-IR780@Ce6 as a sonosensitizer could generate higher levels of reactive oxygen species (ROS) than IR780 and free Ce6 alone, thereby resulting in better anti-cancer effects. Besides, PEG-IR780@Ce6 inhibited the migration and invasion of MDA-MB-231 cells, both in vitro and in vivo, which indicated that it could suppress the metastasis of TNBC. Moreover, the long circulation time and the mitochondria-targeting ability of PEG-IR780@Ce6 guaranteed its accumulation in the tumor. In addition, both in vitro and in vivo experiments indicated the biocompatibility and biosafety of PEG-IR780@Ce6. In conclusion, our results collectively suggested that the newly designed sonosensitizer, PEG-IR780@Ce6, is a promising treatment option for TNBC with excellent therapeutic effects and low side effects.