AUTHOR=Chen Yi-Hsuan , Li Tsung-Ju , Tsai Bo-Yang , Chen Liang-Kuei , Lai Yi-Hsin , Li Meng-Jia , Tsai Cheng-Yang , Tsai Pei-Jane , Shieh Dar-Bin 

TITLE=Vancomycin-Loaded Nanoparticles Enhance Sporicidal and Antibacterial Efficacy for Clostridium difficile Infection

JOURNAL=Frontiers in Microbiology

VOLUME=10

YEAR=2019

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2019.01141

DOI=10.3389/fmicb.2019.01141

ISSN=1664-302X

ABSTRACT=<p>Current antibiotic treatments fail to eliminate the <italic>Clostridium difficile</italic> (<italic>C. difficile</italic>) spores and induce dysbiosis and intestinal inflammation via off-target effect, which causes refractory <italic>C. difficile</italic> infection raise an unmet need for a spore-specific antimicrobial treatment. We developed a sporicidal and antimicrobial vancomycin-loaded spore-targeting iron oxide nanoparticle (van-IONP) that selectively binds to <italic>C. difficile</italic> spores. Cryo-electron microscopy showed that vancomycin-loaded nanoparticles can target and completely cover spore surfaces. They not only successfully delayed the germination of the spores but also inhibited ∼50% of vegetative cell outgrowth after 48 h of incubation. The van-IONPs also inhibited the interaction of spores with HT-29 intestinal mucosal cells <italic>in vitro</italic>. In a murine model of C. difficile infection, the van-IONP significantly protected the mice from infected by <italic>C. difficile</italic> infection, reducing intestinal inflammation, and facilitated superior mucosal viability compared with equal doses of free vancomycin. This dual-function targeted delivery therapy showed advantages over traditional therapeutics in treating <italic>C. difficile</italic> infection.</p>