Aqueous synthesized quantum dots interfere with the NF-kappa B pathway and confer anti-tumor, anti-viral and anti-inflammatory effects

作者:Hu, Zhilin; Song, Bin; Xu, Lei; Zhong, Yiling; Peng, Fei; Ji, Xiaoyuan; Zhu, Fang; Yang, Chengkui; Zhou, Jinying; Su, Yuanyuan; Chen, Suning; He, Yao*; He, Sudan*
来源:Biomaterials, 2016, 108: 187-196.
DOI:10.1016/j.biomaterials.2016.08.047

摘要

The NF-kappa B pathway plays crucial roles in inflammatory responses and cell survival. Aberrant constitutive NF-kappa B activation is associated with various human diseases including cancer and inflammatory and auto immune diseases. Consequently, it is highly desirable to develop new kinds of inhibitors, which are highly efficacious for blocking the NF-kappa B pathway. In this study, by using a typical kind of aqueous synthesized quantum dots (QDs), i.e., CdTe QDs, as a model, we for the first time demonstrated that the QDs could selectively affect the cellular nuclear factor-kappa B (NF-kappa B) signaling pathway, but do not affect the AKT or ERK pathways. Typically, the QDs efficiently inhibited the activation of IKK alpha and IKK beta, resulting in the suppression of both the canonical and the non-canonical NF-kappa B signaling pathways. Inhibition of NF-kappa B by QDs downregulates anti-apoptotic genes and promotes apoptosis in cancer cells. The QDs induced NF-kappa B inhibition and cytotoxicity could be blocked by N-acetylcysteine due to the reduced cellular uptake of QDs. Importantly, inhibition of NF-kappa B by QDs displayed promising effects against the viral replication and in vivo bacterial endotoxin-induced inflammatory responses. These data suggest the QDs as potent inhibitors of the NF-kappa B signaling pathway, both in vitro and in vivo. Our findings highlight the potential of using QDs in the development of anti-cancer, anti-viral, and anti-inflammatory approaches, and also facilitate better understanding of QDs-related cellular behavior under the molecular level.