Zn2+ enhanced the anti-breast cancer activity of fucoidan based nanoparticles by activating the cGAS-STING pathway

The incidence rate of breast cancer remains high, and lung metastasis often leads to treatment failure. Immunotherapy based on the cyclic guanosine monophosphate synthesis (cGAS) − interface gene stimulatory factor (STING) pathway is expected to bring benefits to the treatment of breast cancer. This study provided a delivery system based on fucoidan (Fu) and polyvinylpyrrolidone (PVP) for the potential molecule resveratrol (Res). The study confirmed that Fu and PVP were assembled into nanoparticles through hydrogen bonding and effectively loaded Res (Fu/PVP/Res). Interestingly, the adsorption of Zn 2+ (Fu/PVP/Res Zn 2+ ) was expected to provide impetus for the treatment of breast cancer. The results in vitro confirmed that Fu/PVP/Res Zn 2+ significantly inhibited the proliferation of breast cancer 4T1 cells, induced the accumulation of mitochondrial reactive oxygen species (ROS) and the damage of mitochondrial membrane potential (MMP), and further induced the cytoplasmic release of mtDNA, which was the direct cause of the activation of cGAS-STING pathway. In vivo studies confirmed that Fu/PVP/Res Zn 2+ treatment inhibited the growth of 4T1 transplanted tumors. Excitingly, Fu/PVP/Res Zn 2+ treatment also prevented lung metastasis of in situ tumors. The in vivo mechanism confirmed that Fu/PVP/Res Zn 2+ treatment activated the cGAS-STING pathway and induced abnormal expression of tumor apoptosis factors such as Bax/Bcl-2. In conclusion, our research provided potential for the treatment of breast cancer.