Remote Control of Cellular Localization in the Gastrointestinal Tract Using Magnetic Particles

Engineered probiotics have the potential to diagnose and treat many diseases linked to the gastrointestinal (GI) tract; however, their therapeutic potential is fundamentally constrained by their ability to colonize desired GI niches and specifically respond to endogenous and extrinsic stimuli. As such, a method to non-invasively control the persistence and localization of engineered probiotics can greatly improve therapeutic outcomes for GI linked disorders, in addition to being an important basic-research tool for studying gut microbial communities. Magnetic fields are uniquely suited to address this challenge because of their ability to freely penetrate tissue, however the rapid decay of fields from a magnetic source limits their broader utility for targeting cells within the GI-tract. Here we demonstrate a new approach that uses micromagnets, in concert with an external magnetic-field, in order to enhance the retention of orally administered probiotics in the murine GI tract. We show that this approach enhances the colonization of probiotic E. coli Nissle in mice that were not treated with antibiotics. Our cellular localization assisted by magnetic particles (CLAMP) strategy can potentially be generalized to any cell (bacterial, mammalian) or drug-containing nanoparticle of interest, and can also be combined with existing non-invasive imaging modalities, thereby facilitating remote control and sensing of engineered cells at sites of interest in vivo.