Characterization and Optimization of Nanoparticle Targeting to Bacteria Cell Wall Components

Abstract

Antibiotic resistant infections significantly increase health and economic burdens. In the fight against antibiotic resistance, polymeric nanoparticles are an attractive approach as the particles can be functionalized for targeted drug delivery to maximize therapeutic efficacy. In order to target infections, the targeting moieties zinc(II)-bis(dipicolylamine) (Zn-DPA), galactose, and vancomycin were explored as surface modifications of nanoparticles, and the effects on bacterial cell binding of modified particle properties were studied. Nanoparticles functionalized with the targeting moieties were formed with Flash NanoPrecipitation, and particle properties were characterized. Targeted particles were then incubated with different bacteria to investigate the level of cell binding. As for Zn-DPA nanoparticles, it was determined that the amount of surface modification had only a small effect on particle size and that the surface charge is proportionally related to the level of surface modification. It was found that greater surface modification allowed for improved cell binding, and that smaller and larger particles allowed for greater binding than intermediate sized particles. In addition, Zn-DPA particles demonstrated the ability to bind to and remove bacteria from liquid solutions, which has important health-related implications in filtering out pathogens from drinking water and septic bloodstreams. Lastly, galactose and vancomycin particles were explored briefly and found to bind to bacteria at level lowers than Zn-DPA particles. These findings are the first quantitative study of how changing Zn-DPA surface modification levels and particle size affects targeting on bacteria. These results provide a guideline for designing optimal particle formulations to achieve the desired targeting behaviors.