Single-Cell Nanoencapsulation of Probiotics within Fe3+-Trimesic Acid Nanoshells for Effective Cytoprotection against Gastrointestinal Insults

Abstract Probiotic oral delivery is constrained by harsh gastrointestinal conditions and antibiotic exposure. This paper presents a single-cell nanoencapsulation strategy that assembles protective Fe3+-benzene-1,3,5-tricarboxylate (BTC; trimesic acid) metal—organic nanoshells around individual probiotics, including Lactobacillus acidophilus, to create cell-in-shell nanobiohybrids. Nanoencapsulated cells exhibit markedly enhanced viability relative to native counterparts under diverse gastrointestinal stressors. Under strongly acidic conditions (pH 2.0), cell-in-shell nanobiohybrids retain 7.45 log CFU/mL after 3 h, compared with 6.00 log CFU/mL for native cells, while maintaining 7.09 log CFU/mL in simulated gastric fluid where native cells are completely inactivated. Enhanced tolerance is also observed under tetracycline exposure (7.59 vs 7.00 log CFU/mL) and bile salts-trypsin treatment (6.88 vs 4.00 log CFU/mL). The Fe3+-BTC nanoshells provide a cytocompatible platform that enhances probiotic resilience against multiple gastrointestinal stressors and is broadly applicable to other therapeutically relevant cells.