Introducing HaNTr – Halloysite Nanotubes Targeting System for The Selective Delivery of Antibiotics

Antibiotics have been established to induce indiscriminate detrimental effects on the gut commensal bacteria which are vital for human health. This study unprecedently reports the mitigation of this challenge through the targeted delivery of antibiotics to a specific intestinal model pathogen using naturally occurring nanoclay. The designed Halloysite nanotubes targeting (HaNTr) system employs intrinsically mesoporous clay particles, functionalized with antibodies against Escherichia coli (E. coli). Loaded with the antibiotic ciprofloxacin (CIP), the HaNTr particles demonstrate enhanced selectivity of their payload in a human microbiome ex vivo system, preserving the composition of non‐target populations. Furthermore, the HaNTr system exhibits up to a 10‐fold increase in selectivity against E. coli, compared to neat CIP, in a heterogenous culture. This enhanced selectivity is attributed to the sustained and localized release of CIP from the HaNTr particles (≈0.8 ng CIP min−1 mg−1), following their specific binding to target bacteria, as quantitatively measured by high‐throughput imaging flow cytometry. Importantly, HaNTr particles are also shown to be biocompatible with Caco‐2 cells, mimicking the intestinal epithelium. This work highlights the prominent capability of the HaNTr system in alleviating antibiotic‐associated dysbiosis by the targeted delivery of antimicrobials to potentially any microorganism against which the immobilized capture probe can be customized. Natural Halloysite nanotubes are utilized to alleviate the inadvertent collateral damage of antibiotics to vital gut bacteria. Antibodies, conjugated onto the silica surface of the nanoclay, endow it with targeting capabilities, while the mesoporosity enables the sustained release of an antibiotic payload near the bound bacteria, demonstrating enhanced selectivity in an ex vivo model of the human microbiome.