Premna microphylla Turcz pectin-modified diosmetin nanoparticles: A galectin-3 targeting strategy for precise colitis intervention

Oral delivery of natural antioxidants represents a promising therapeutic strategy for ulcerative colitis (UC), yet their therapeutic efficacy is hindered by instability and poor accumulation at inflamed sites. To address this, we developed Galectin-3 (Gal-3)-targeted nanoparticles (ZDP-NPs) by encapsulating diosmetin within zein complexes modified with a galactose- and rhamnogalacturonan-I (RG-I)-rich pectin (PMTP, Mw: 228.8 kDa, DM: 34.21 %, RG-I content: 43 %) extracted from Premna microphylla Turcz leaves. Surface plasmon resonance (SPR) analysis confirmed a strong binding affinity between PMTP and Gal-3 (KD = 2.83 μM). ZDP-NPs exhibited uniform spherical morphology (~170 nm), high drug loading (87.9 %) and colloidal stability. Under simulated gastrointestinal conditions, ZDP-NPs showed reduced Dio release (45.6 %) compared to PMTP-free nanoparticles (ZD-NPs, 75.6 %). In vitro studies showed that PMTP surface modification significantly enhanced nanoparticle uptake by LPS-induced macrophages via Gal-3-mediated endocytosis. In vivo colitis experiment of mice revealed that ZDP-NPs selectively accumulated in inflamed colons via Gal-3 targeting, prolonged retention, and significantly alleviated colonic damage by reducing oxidative stress, suppressing pro-inflammatory cytokines, and restoring epithelial barrier integrity. Biocompatibility assays confirmed minimal toxicity of ZDP-NPs. This study presented a food-derived pectin-based nanoplatform for precise colitis intervention through Gal-3 targeting, offering a multifaceted strategy to break the inflammation-oxidative stress cycle.