pH‐Responsive Probiotic‐Liposome Hybrid System Synergistically Treats Radiation‐Induced Injury via Dual Mechanisms of Anti‐Inflammatory and Microbiome Modulation

Radiation-induced intestinal injury poses significant clinical challenges in radiotherapy. This study develops an oral pH-responsive probiotic-liposome hybrid system (EcN^PIN-L) by conjugating Escherichia coli Nissle 1917 (EcN) with pinocembrin (PIN)-loaded liposomes (B-Lip-PIN) via biotin-streptavidin binding and encapsulating them in Eudragit L100-55 (L100-55). The system resists gastric acid, releases bacteria in intestinal pH conditions, and combines PIN's anti-inflammatory properties with EcN's probiotic effects. In irradiated mice, EcN^PIN-L demonstrates effective intestinal colonization and multiple therapeutic benefits: it reduces pro-inflammatory cytokines (TNF-α, IL-17A), enhances intestinal barrier function, and decreases epithelial apoptosis. 16S rRNA sequencing reveals improved microbiota homeostasis with increased beneficial bacteria and decreased harmful species. The system shows superior efficacy compared to individual components, addressing both inflammatory damage and microbial dysbiosis while maintaining biocompatibility. These results highlight EcN^PIN-L as a promising dual-mechanism therapy for radiation-induced intestinal injury, offering targeted delivery and combined anti-inflammatory/microbiome-modulating action.