Directed transport of bacteria-based drug delivery vehicles: bacterial chemotaxis dominates particle shape
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Several attenuated and non-pathogenic bacterial species have been demonstrated to actively target diseased sites and successfully deliver plasmid DNA, proteins and other therapeutic agents into mammalian cells. These disease-targeting bacteria can be employed for targeted delivery of therapeutic and imaging cargos in the form of a bio-hybrid system. The bio-hybrid drug delivery system constructed here is comprised of motile Escherichia coli MG1655 bacteria and elliptical disk-shaped polymeric microparticles. The transport direction for these vehicles can be controlled through biased random walk of the attached bacteria in presence of chemoattractant gradients in a process known as chemotaxis. In this work, we utilize a diffusion-based microfluidic platform to establish steady linear concentration gradients of a chemoattractant and investigate the roles of chemotaxis and geometry in transport of bio-hybrid drug delivery vehicles. Our experimental results demonstrate for the first time that bacterial chemotactic response dominates the effect of body shape in extravascular transport; thus, the non-spherical system could be more favorable for drug delivery applications owing to the known benefits of using non-spherical particles for vascular transport (e.g. relatively long circulation time).
KeywordsBacteriaBots Drug delivery Bacterial chemotaxis Microfluidics Particle shape
The authors would like to acknowledge Brian Geuther for helping with the developing of the graphics and Ivan Morozov for the photographs of the device. Our gratitude also goes to our other colleagues in the MicroN BASE laboratory at Virginia Tech especially Meghan A. Canter for helping with particle stretching. This work was in part supported by the National Science Foundation (IIS-117519).
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