Engineered silk fibroin dendritic cell backpacks to boost antitumor immunity following radiotherapy.

Abstract

Radiotherapy initiates an antitumor immune response by releasing tumor antigens; however, its efficacy is often limited by the subsequent quantitative and qualitative dysfunction of dendritic cells within the tumor microenvironment. This dysfunction leads to impaired antigen presentation and suboptimal T cell activation. To address this, we developed a biomaterial-based cellular engineering strategy using silk fibroin-based dendritic cell backpacks. Silk fibroin backpacks offer structural stability and aqueous processability, enabling the incorporation of CpG under mild conditions. The easy functionalization of silk fibroin allows hydrophobic modifications on the backpack surface, enabling covalent grafting of hydrophobic chains onto the BP surface and promoting stable association with the DC membrane through hydrophobic intercalation. These backpacks preserve dendritic cell function while providing sustained local delivery of immune signals. This platform integrates material design with cellular immunoengineering to overcome a key barrier in post-radiation immunity, presenting a versatile strategy to enhance dendritic cell function and synergize with radiotherapeutic modalities for more durable antitumor immunity.