Photo-triggered NO combined with photobiomodulation promotes endothelial repair after balloon angioplasty

Balloon angioplasty, though effective for vascular stenosis, inevitably induces endothelial injury during dilation and clinical strategies to actively promote intimal repair remain lacking. Photobiomodulation (PBM) has demonstrated promising effects in tissue repair through its potent biological regulatory functions. Meanwhile, light is also a particularly appealing tool for drug delivery due to its strong spatiotemporal controllability. In this study, we developed a red light-triggered nitric oxide (NO) releasing coating based on the photosensitive NO donor S-Nitroso-N-acetyl-DL-penicillamine (SNAP). The coating enabled on-demand NO release under red light irradiation, modulating cellular signaling pathways to guide functional endothelial repair. After releasing NO, the SNAP coating significantly promoted endothelial cell (EC) migration and proliferation, while suppressing smooth muscle cell (SMC) activity, resulting in an increase in the EC/SMC ratio by 0.48 in co-culture. In vivo experiments, the combined effect of PBM and light-controlled drug release alleviated vascular inflammation and reduced restenosis (intimal hyperplasia decreased by 63 μm), demonstrating superior therapeutic efficacy compared to PBM alone.