Visible light accelerates skin wound healing and alleviates scar formation in mice by adjusting STAT3 signaling.

During the wound healing process, the activation of signal transducer and activator of transcription 3 (STAT3) is considered crucial for the migration and proliferation of epithelial cells, as well as for establishing the inflammatory environment. However, an excessive STAT3 activation aggravates scar formation. Here we show that 450 nm blue light and 630 nm red light can differentially regulate the phosphorylation of STAT3 (p-STAT3) and its downstream cytokines in keratinocytes. Further mechanistic studies reveal that red light promotes wound healing by activating the PI3 kinase p110 beta (PI3Kß)/STAT3 signaling axis, while blue light inhibits p-STAT3 at the wound site by modulating cytochrome c-P450 (CYT-P450) activity and reactive oxygen species (ROS) generation. In a mouse scar model, skin wound healing can be significantly accelerated with red light followed by blue light to reduce scar formation. In summary, our study presents a potential strategy for regulating epithelial cell p-STAT3 through visible light to address skin scarring issues and elucidates the underlying mechanisms.

Blue light promotes vitamin C-mediated ferroptosis of melanoma through specifically upregulating transporter SVCT2 and generating Fe2.

Vitamin C (VC)-based cancer therapy is a promising therapeutic approach for a variety of cancers due to its profound effects on redox reactions and metabolic pathways. However, high administration dosage of VC for necessary therapeutic efficacy for cancers increases the risk of overt side effects and limits its clinical use. Here, we show cutaneous blue light irradiation can specifically upregulate the sodium-dependent vitamin C transporter 2 (SVCT2) of the tumor and increase effectively the VC concentration at the tumor sites by an overall low dosage administration. In the mouse melanoma model, blue light stimulates the SVCT2 expression through the nuclear factor-kappa B (NF-κB) signaling pathway both in vitro and in vivo. The increased cellular VC together with Fe2+ generated by blue light simultaneously elevate cellular oxidative stress and trigger the ferroptosis of melanoma. With this revealed mechanism, the synergistic actions of blue light on the VC transporter and Fe2+ generation lead to a ca. 20-fold reduction in the administration dosage of VC with an effective melanoma elimination and prolonged survival. The work defines the killing mechanism of blue light on VC-based cancer therapy and provides a practical approach for promoting VC uptake. This light-assisted VC therapy is not only highly efficient for melanoma but also considerable for a broad clinical utility.