Electrostatic Assembly of Ginseng Polysaccharides and Chito-Oligosaccharides to Enhance Dendritic Cell-Mediated Antigen Priming for Synergistic Radio-Immunotherapy

Radiotherapy (RT) is inherently capable of eliciting antitumor immunity; yet, its systemic potential remains largely unexploited due to a critical disconnect between local immunogenic cell death and efficient immune priming. To bridge this gap, we designed a strategic nanoassembly of ginseng polysaccharides (GP) and chito-oligosaccharides (COS) to serve as a priming-booster that bridges local radiotherapy with systemic immune responses. This strategy leverages the intrinsic bioactivity of these polysaccharides to optimize surface charge, facilitating their targeted uptake by antigen-presenting cells (APCs). Our results demonstrate that the nanocomplex significantly boosts dendritic cells (DCs) maturation and antigen cross-presentation. Importantly, the assembly itself does not directly activate T cells, confirming that its therapeutic effect stems from the specific enhancement of DC-mediated antigen priming rather than nonspecific immune stimulation. In a murine 4T1 breast cancer model, this nanoassembly synergizes with RT to potently inhibit primary tumor growth and suppress pulmonary metastasis. Mechanistic studies reveal that the treatment orchestrates a profound "cold-to-hot" tumor transformation, characterized by the activation of DCs priming niches, increased CD8⁺ T cell infiltration, and multipronged M1-like macrophage repolarization. This work offers a sophisticated strategy to convert local radiotherapy into a systemic in situ vaccination hub, effectively amplifying the abscopal effect through refined immune priming.