Janus nanomotors for topical treatment of radiation-induced dermatitis.

Topical treatment remains the standard for radiation-induced dermatitis, which affects approximately 95% of radiotherapy patients. However, the robust skin barrier significantly restricts transdermal drug permeability, compromising therapeutic efficacy. Here we show a NIR-Ⅱ light and endogenous H2O2 dual-propelled Janus nanomotor (Au-hSiO2-Pt-TA), which enhances skin permeability by a factor of 12.8 compared with passive nanoparticles. By leveraging the synergistic advantages of self-thermophoresis and self-electrophoresis, these motors enable non-invasive, deep penetration through directional movement. Intriguingly, we find that NIR-II-induced hyperthermia (~ 45 °C) triggers neuro-immune regulation via the CGRP-RAMP1 axis, which suppresses inflammatory cell recruitment and migration while polarizing macrophages toward a pro-repair phenotype, thereby alleviating radiation-induced systemic inflammatory responses. Additionally, tannic acid loaded on the nanomotors functions as an efficient ROS scavenger, further mitigating radiation-induced oxidative stress. Overall, the movable nanomotors offer a potent strategy for RD and demonstrate high efficacy through combined neuro-immunoregulation and ROS scavenging.