NIR-II light based combinatorial management of hypertrophic scar by inducing autophagy in fibroblasts
Yunxian Dong, Hai‐Bin Wang, Youliang Zhang, Yanqun Wu, Ling Lü, Hao Yu, Lingcong Zhou, Peng Zhao, Sixue Ouyang, Zibin Song, Zhicheng Hu, Dongming Lv, Yanchao Rong, Zirui Zhao, Jia Tao, Bing Tang, Sheng‐Kang Luo
Abstract
The hypertrophic scar (HS) is a prevalent cutaneous fibrotic disorder that impacts both the aesthetic and functional aspects of the skin, there is an urgent need for a highly safe and effective approach to address the challenge of HS with thick and deep types. Inspired by the superior deep tissue penetrative ability of near-infrared-II (NIR-II) light and potential mitochondria ROS inducing effect of Chinese medicine lycorine (LYC), we fabricated a Cu 2 Se@LYC (CL) composite by encapsulating LYC on polyvinyl pyrrolidone (PVP) modified Cu 2 Se nanoparticles. After NIR-II irradiation, CL could induce the generation of reactive oxygen species (ROS) and mitochondrial damage in hypertrophic scar fibroblasts (HSFs). The subsequent release of cytochrome C (cyt-c) from mitochondria into the cytoplasm and upregulation of beclin1 leads to the activation of endogenous apoptosis and autophagy-mediated cell death. The CL + NIR-II treatment exhibited a pronounced anti-scarring effect in both in vitro and in vivo rabbit ear scar models, leading to a significant reduction in the fibrotic markers including Collagen I/III and α-smooth muscle actin (α-SMA). This study comprehensively investigated the crucial role of HSFs’ autophagy in scar management and proposed a safe and effective therapy based on NIR-II laser for clinical application.