Synergistic Combination of Oral Transcytotic Nanomedicine and Histone Demethylase Inhibitor for Enhanced Cancer Chemoimmunotherapy

Oral nanomedicines present a preferable avenue for cancer immunotherapy, but their efficacy is limited by gastrointestinal absorption challenges, tumor physiopathologic barriers, and immune evasion mechanisms. Here, we present an approach that combines an oral transcytotic doxorubicin (DOX) nanomedicine with the histone demethylase inhibitor 5-carboxy-8-hydroxyquinoline (IOX1), thereby enabling synergistic chemoimmunotherapy. We demonstrate that IOX1 significantly augments the transcytosis capabilities of DOX-loaded poly(2-(