Photothermogenetic inhibition of cancer stemness by near-infrared-light-activatable nanocomplexes

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/beta -catenin signalling pathway. The present technological concept may lead to innovative therapies to address the global issue of refractory cancers. Cancer stem cells (CSCs) are known to induce chemotherapy resistance, and cause tumour relapse and metastasis. Here, the authors develop photoactive nanocarbon complexes with second near-infrared photothermal ability to target cancer cells overexpressing the receptor TRPV2 and show it to suppress CSCs through dysregulation of the Wnt/beta -catenin signalling pathway.