Bilayer nanofiber-coated stent integrating internal radiation and spatiotemporal IL-12 release promotes antitumor immune response

Abstract

Internal radiation (IR), utilizing iodine-125 (¹²⁵I) seeds as a radiation source, is a clinically established modality for targeted treatment of malignant tumors. In addition to inducing DNA damage in tumor cells, IR therapy can trigger systemic antitumor immune responses, known as the abscopal effect, through immunogenic cell death (ICD). However, the gradual decline in radioactive output and the inherently limited immunogenicity of IR therapy compromise its overall efficacy, with the abscopal effect rarely observed in clinical settings. To overcome these challenges, we developed a bilayer nanofiber-coated stent integrating ¹²⁵I seed-based brachytherapy with sustained, spatiotemporally controlled delivery of interleukin-12 (IL-12). Utilizing FDA-approved PLGA and PEO polymers, the inner layer was engineered for IL-12 loading, while the outer layer acted as a regulatory barrier, achieving a biphasic release profile with sustained cytokine delivery for up to 14 days. In vivo studies demonstrated that the IL-12@IRS (IL-12-loaded ¹²⁵I internal radiation stent) effectively enhanced antigen presentation and elicited a tumor in situ vaccination effect, thereby promoting durable local and systemic antitumor immunity. This immuno-radiotherapeutic platform not only improves local tumor control but also offers a promising strategy for overcoming immune resistance and inducing robust systemic antitumor effects.