Oral Administration of Nanoiron Sulfide Supernatant for the Treatment of Gallbladder Stones with Chronic Cholecystitis

作者：Liming Ding, Jian Jiang, Lu Cheng, Yanqiu Wang, Wei Zhang, Dandan Li, Zhuobin Xu, Jing Jiang, Lizeng Gao, Zhennan Li · 发表于：ACS Applied Bio Materials · 年份：2020 · DOI：10.1021/acsabm.0c01258 · 被引用次数：18 · 研究领域：Trace Elements in Health、Iron Metabolism and Disorders、Cassava research and cyanide

Cholelithiasis with chronic cholecystitis is prevalent and threatens human health. Most cholecystitis caused by bacterial infection or biofilms is accompanied by gallstones in the clinic, making gallbladder removal the only effective solution. Here, we provide a strategy to eliminate gallstone biofilms and dissolve gallstones by oral administration of a supernatant derived from nanoscale iron sulfide (nFeS supernatant). First, by using gallstones obtained from the clinic, we simulated biofilm formation on gallstones and tested the antibacterial activity of a nFeS supernatant in vitro . We found that the supernatant kills bacteria with a 5-log reduction in viability and destroys the biofilm structure. Smashed gallstones coincubated with E. coli biofilms promote gallstone formation, while nFeS supernatant can inhibit this process. Second, by using a murine (C57BL/6) model of cholelithiasis and cholecystitis, we tested the antibacterial efficacy and therapeutic effects of nFeS supernatant on cholelithiasis in vivo . Animal experimental data show that oral administration of nFeS supernatant can reduce 60% of bacteria in the gallbladder and, remarkably, remove gallstones with 2 days of treatment compared with clinical drug combinations (chenodeoxycholid acid and ciprofloxacin). Third, by performing protein abundance analysis of L02 cells and mouse livers, we observed the changes in CYP7a1, HMGCR, and SCP2 expression, indicating that the nFeS supernatant can also regulate cholester...