Nanoparticle Adjuvants Incorporating Haptens Drive Potent Immune Tolerance to Accelerate Hair Regrowth.

Alopecia areata (AA) is a prevalent autoimmune condition that causes sudden hair loss and poses significant psychological challenges to affected individuals. Current treatments, including corticosteroids and Janus kinase inhibitors, fail to provide long-term efficacy due to adverse effects and relapse after cessation. This study introduces a nanoparticle (NP) system that codeliver diphenylcyclopropenone (DPCP) and rapamycin (RAPA) prodrugs to induce immune tolerance and promote hair regeneration. The results demonstrated that the coassembled NPs exhibited uniformity and stability, were efficiently taken up by antigen-presenting cells (APCs), and successfully induced dendritic cells (DCs) to differentiate into tolerogenic phenotypes in vitro. In vivo studies on a mouse model of alopecia showed that these NPs significantly accelerated the transition of hair follicles from the telogen phase to the anagen phase, promoting hair regrowth. This research presents a promising therapeutic strategy for AA and offers insights into treating autoimmune diseases where autoantigens are unclear.