Graduate School of Advanced Science and Technology, Japan Advanced Institute of Science and Technology, 1-1 Asahidai, Nomi, Ishikawa, 923-1292, Japan.
Biomedical Research Institute, National Institute of Advanced Industrial Science & Technology (AIST), Ikeda, 563-8577, Japan.
Nat Commun. 2020 Aug 17;11(1):4117. doi: 10.1038/s41467-020-17768-3.
Strategies for eradicating cancer stem cells (CSCs) are urgently required because CSCs are resistant to anticancer drugs and cause treatment failure, relapse and metastasis. Here, we show that photoactive functional nanocarbon complexes exhibit unique characteristics, such as homogeneous particle morphology, high water dispersibility, powerful photothermal conversion, rapid photoresponsivity and excellent photothermal stability. In addition, the present biologically permeable second near-infrared (NIR-II) light-induced nanocomplexes photo-thermally trigger calcium influx into target cells overexpressing the transient receptor potential vanilloid family type 2 (TRPV2). This combination of nanomaterial design and genetic engineering effectively eliminates cancer cells and suppresses stemness of cancer cells in vitro and in vivo. Finally, in molecular analyses of mechanisms, we show that inhibition of cancer stemness involves calcium-mediated dysregulation of the Wnt/β-catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers.
由于癌症干细胞 (CSC) 对抗癌药物具有耐药性，并导致治疗失败、复发和转移，因此迫切需要消除 CSC 的策略。在这里，我们表明光活性功能纳米碳复合物具有独特的特性，例如均匀的颗粒形态、高水分散性、强大的光热转换、快速光响应性和优异的光热稳定性。此外，目前具有生物渗透性的第二代近红外 (NIR-II) 光诱导纳米复合物光热可引发过度表达瞬时受体电位香草素家族 2 型 (TRPV2) 的靶细胞内钙离子内流。这种纳米材料设计和基因工程的结合可有效消除体外和体内的癌细胞并抑制癌细胞的干性。最后，在机制的分子分析中，我们表明，抑制癌症干性涉及钙介导的 Wnt/β-连环蛋白信号通路的失调。这一技术概念可能为解决全球难治性癌症问题带来创新疗法。
