Spatial Control of Probiotic Bacteria in the Gastrointestinal Tract Assisted by Magnetic Particles

Abstract

segments of the tract after oral administration can reduce efficacy. [3] A method to non-invasively localize and retain bacteria at specified locations could greatly facilitate the development and application of GI probiotics. [3,4] Here we introduce cellular localization assisted by magnetic particles (CLAMP)-an approach that uses locally amplified magnetic fields to provide noninvasive spatial control of cells within the GI tract. This approach takes advantage of the ability of magnetic fields to penetrate biological tissue and exert force on magnetic objects, as has been shown in numerous studies. In previous work, magnetic fields have been used to localize therapeutic mammalian cells and magnetotactic bacteria to tumors, [7][8][9] enhance site-specific cellular uptake of viral vectors or drug-containing liposomes, [10,11] pattern tissues, [12][13][14][15] and remotely control microrobots in vivo. [16] However, while these approaches were effective for heavily iron-loaded cells or nanoparticles, they are challenging to apply to common probiotic bacterial species in the GI tract. This challenge arises fundamentally from the difficulty of creating a sufficiently strong magnetic force to overcome viscous drag forces at the desired location of magnetic manipulation within the GI tract. The force on a magnetized (e.g., superparamagnetic) particle or cell is a product of the local magnetic field (B) and magnetic field gradient (∇B) (Equation 1), [17] which decay rapidly in space as 1/r 3 and 1/r 4 , respectively.

Intestinal Engineered Probiotics as Living Therapeutics: Chassis Selection, Colonization Enhancement, Gene Circuit Design, and Biocontainment

“…This strategy can achieve targeted adhesion to muc2, which can help EcN to colonize more quickly and prolong colonization time . Still further, this method has been applied to magnetic particles to develop cellular localization assisted by magnetic particles (CLAMP) technology, which endows probiotics with magnetotaxis …”

Material Engineering in Gut Microbiome and Human Health

“…By controlling the magnetic field, bacteria can then be localized to specific regions of the gut. One such approach is known as “cellular localization assisted by magnetic particles (CLAMP),” which has been used to deliver magnetic nanoparticle-labeled E. coli [ 268 ]. Although their spatial resolution is suboptimal in small animal models, only allowing accumulation of bacteria in the small intestine, they may be useful for human clinical trials given the larger sizes of the human GI tract and may also be suitable for targeting disease states limited to the small intestine.…”

Engineering Cell‐Based Systems for Smart Cancer Therapy

“…[ 205 ] This strategy requires the integration of magnetic nano/microparticles into the living system. Magnetic particles conjugated onto the surface of bacteria such as E. coli [ 206,207 ] and Serratia marcescens [ 208 ] conferred the ability to align with magnetic fields, with swimming velocities lower than that of sole bacteria. Microswimmers created by attaching several E. coli to multilayer microparticles loaded with doxorubicin and magnetite were demonstrated to have mean swimming speeds of up to 22.5 μm s −1 and to deliver doxorubicin in 4T1 breast cancer cells in vitro under a chemoattractant gradient and a magnetic field.…”