Near-infrared light-triggered nitric oxide-releasing hyaluronic acid hydrogel for precision transdermal therapy of androgenic alopecia

Progressive follicle and vascular atrophy, insufficient nutrient supply, and hormonal imbalance are direct causes of androgenic alopecia (AGA), limiting treatment options. Nitric oxide (NO) has demonstrated significant advantages in cell proliferation, vascular repair, and inflammation regulation. However, precise control of NO concentration and efficient utilization limit its clinical application for AGA treatment. To address this, we developed a near-infrared (NIR) light-triggered NO-releasing delivery system (Gel@L-Arg). The system uses Chlorin e6 (Ce6) grafted onto oxidized hyaluronic acid, reacting with L-Arg-loaded polyethyleneimine via Schiff base to form hyaluronic acid hydrogel. Under NIR light, Ce6 generates ROS, oxidizing L-Arg to release NO, after 5 min of irradiation, the NO concentration in Gel@L-Arg (1 %) is >1.5 times that in Gel@L-Arg (0.5 %), enabling on-demand release of NO. Gel@L-Arg (0.5 %) effectively promotes angiogenesis while significantly repairing damaged human dermal papilla cells (HDPCs), with cell viability reaching 131.6 +/- 4.6 %. In animal models, the system reduced inflammation (IL-6, TNF-alpha), enhanced nutrient supply (VEGF, CD31), regulated androgens, and improved the follicular microenvironment, effectively treating AGA. This hyaluronic acid hydrogel, combining NIR light-triggered release with gas therapy, offers a new strategy for the treatment of AGA with good biocompatibility, providing insight into controlled gas release therapies for disease treatment.