Abstract

Biocompatible nanoparticles hold a great promise for biomedical applications, whereas their biosafety has raised extensive concerns. Nanodiamonds (NDs) are generally regarded as “inert” nanocarriers and widely employed in biomedical studies; however, it is yet to explore their biological effects in more general contexts. In this study, the authors observe that intracellular NDs block signal transduction of the Wnt signaling pathway, an effect that is not caused by general cytotoxicity. The authors find that NDs attenuate activities of Wnt signaling in several types of cell lines and in Zebrafish, and interfere with Wnt signaling-controlled biological processes, including cancer cell migration, adipocyte differentiation, and embryonic development. Significantly, the authors show that intracellular NDs trigger degradation of the disheveled protein, a key component of Wnt signaling cascade, while they do not affect protein stability of other Wnt signal transducers or other signaling molecules. This work thus illustrates a novel crosstalk between nanoparticles and the Wnt signaling pathway, and expands the understanding of biological effects induced by nanoparticles. In addition, given the clinical implications of Wnt signaling in tumorigenesis and cancer metastasis, this study also provides the rationale for potential applications of NDs in cancer therapies.

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