Nanodiamonds Interfere with Wnt-Regulated Cell Migration and Adipocyte Differentiation in Cells and Embryonic Development In Vivo
Nanodiamonds Interfere with Wnt-Regulated Cell Migration and Adipocyte Differentiation in Cells and Embryonic Development In Vivo
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纳米金刚石干扰 Wnt 调节的细胞迁移和脂肪细胞分化以及体内胚胎发育
DOI：
10.1002/ppsc.201600208
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发表时间：
2017
影响因子：
2.7
通讯作者：
Song Haiyun
中科院分区：
文献类型：
--
作者：
Yi Hongyang;Li Xiaojiao;Wang Zhuyao;Yin Min;Wang Lihua;Aldalbahi Ali;El-Sayed Nahed Nasser;Wang Hui;Chen Nan;Chen Luonan;Fan Chunhai;Song Haiyun
生物相容纳米颗粒在生物医学领域有着广阔的应用前景，但它们的生物安全性却引起了广泛关注。纳米钻石(NDS)通常被认为是“惰性”纳米载体，被广泛用于生物医学研究；然而，在更广泛的背景下还没有探索它们的生物学效应。在这项研究中，作者观察到细胞内NDS阻断了Wnt信号通路的信号转导，这一效应不是由一般的细胞毒性引起的。作者发现，NDS减弱了Wnt信号在几种类型的细胞系和斑马鱼中的活性，并干扰了Wnt信号控制的生物过程，包括癌细胞迁移、脂肪细胞分化和胚胎发育。值得注意的是，作者们表明，细胞内的NDS会触发Wnt信号级联的关键成分--蓬乱的蛋白质的降解，而它们不会影响其他Wnt信号转导或其他信号分子的蛋白质稳定性。因此，这项工作阐明了纳米颗粒和Wnt信号通路之间的一种新的串扰，并扩大了对纳米颗粒诱导的生物效应的理解。此外，鉴于Wnt信号在肿瘤发生和癌症转移中的临床意义，本研究也为NDS在癌症治疗中的潜在应用提供了理论基础。
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.