Off-the-shelf microbrachytherapy using on-site fast radiolabeling for keloid treatment

Keloids are fibroproliferative dermal tumors caused by aberrant healing after skin injury and represent refractory skin conditions with limited therapeutic options that often require prolonged treatment. Although radiotherapy lowers recurrence, external beams struggle to confine doses to small, irregular lesions. Herein, we report an off-the-shelf microbrachytherapy approach that uses on-site radiolabeled microgels for keloid treatment. Through absorption-mediated rapid labeling of radioactive iodine-131 (¹³¹I) to uniform freeze-dried microgels prepared from hyaluronic acid (HA) with radiolabeling functional groups, injectable radioactive biodegradable HA microgels were developed with high radiolabeling efficiency (> 90% within 10 min) and excellent labeling stability (> 98% of expected radioactivity). In a keloid xenograft model using patient-derived keloid tissues, intralesionally injected ¹³¹I-labeled HA microgels significantly reduced keloid size (70% in 2 weeks) without off-target biodistribution or damage to surrounding healthy tissues. This on-site rapid radiolabeling platform for preparing radioactive microgels provides a straightforward and universal approach to the development of user-demanded, programmed, off-the-shelf local radiotherapies.