Functionalized Ionic Liquid Nanoparticles Target <i>E. coli</i> in Whole Blood

Septicemia remains a critical clinical challenge, even with conventional antibiotic therapies available. Severe infections signal opportunistic microbes to trigger overreactive immune responses, leading to the downward cascade of tissue damage and organ failure generally associated with sepsis. However, increasing multidrug antibiotic resistance further exacerbates the threat of these contaminations, emphasizing the need for therapeutics that act independently of targeting metabolic processes of the bacteria. Extracorporeal devices have been previously studied for their potential in blood cleansing therapies without the need for pathogen identification; however, apparatuses of this kind have not shown great success in translation to the physiological environment. Herein, we propose choline carboxylate ionic liquid-coated polymeric nanoparticles (IL-NPs) as a therapeutic for E. coli binding in whole blood, where the mechanism of action hinges on the IL-NPs labeling bacterial cells for an enhanced immune response to infection. IL-NPs maintain suitable red blood cell (RBC) hemocompatibility up to 40% v/v in both human and mouse blood, while the identity of the anionic moiety drives the selective bacterial binding. Treating E. coli with IL-NPs delays the initiation of the logarithmic growth phase due to the attachment of IL-NPs to the outer structures of the bacterial surfaces. The tunability of the ILs allows for the development of materials with preferential binding affinity toward E. coli cells and adaptable immune responses for the clearance of the captured microbes while maintaining minimal toxicity to mammalian cells. Future applications of the work discussed here will assess the efficacy of IL-NPs for bacterial labeling for enhanced pathogen removal in induced septicemic models in vivo.