Regulations of Nanotechnology

Biography

Biography: Dar-Bin Shieh

Abstract

Clostridium difficile infection (CDI) has emerged to be an important cause of global healthcare-associated infection. Resistance of CD spores to various preventive and therapeutic measures post a significant threat in CDI. Nanomaterials have been explored for potential applications in anti-microbials with intrinsic advantages of low drug-resistance issue and high efficacy. We discovered the 22 nm octahedral Fe3-δO4 single crystal nanoparticles with a strong inhibitory effect to CD spore germination in vitro and in vivo. The nanocrystals presented excellent saturation magnetization (94emu/g) close to the bulk due to the presence of alpha iron. Such particle showed a dose dependent inhibition of CD spores germination (62% growth inhibition at 50 μg/mL) for 20 minutes of exposure. At 500 μg/mL, the inhibition rate is close to that of sodium hypochloride. CDI animal model established in NF-κB-reporter mice using oral gavage with CD spores presented significant bowel inflammation in the MOCK compared to Fe3-δO4 nanoparticle treated group as revealed by in vivo imaging system. Slayer protein and a conserved hypothetical protein were released from CD spores after for 20 minutes of Fe3-δO4 nanoparticle exposure. Cryo-electron tomography clearly showed binding of the nanoparticles to CD spores’ surface followed by disruption of the spores. Pro-inflammatory cytokines including IL-1β, TNF-α, and INF-γ and inflammatory cell infiltrations were significantly suppressed after nanoparticle treatment. These results provide nano-material based strategy for CDI control and potential therapeutic mechanisms that encourage further clinical translational development.