Mesoporous Silica Nanoparticles with pH-Sensitive Nanovalves for Delivery of Moxifloxacin Provide Improved Treatment of Lethal Pneumonic Tularemia
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- 作者：Zilu Li ; Daniel L. Clemens ; Bai-Yu Lee ; Barbara Jane Dillon ; Marcus A. Horwitz ; Jeffrey I. Zink
- 刊名：ACS Nano
- 出版年：2015
- 出版时间：November 24, 2015
- 年：2015
- 卷：9
- 期：11
- 页码：10778-10789
- 全文大小：715K
- ISSN：1936-086X
文摘
We have optimized mesoporous silica nanoparticles (MSNs) functionalized with pH-sensitive nanovalves for the delivery of the broad spectrum fluoroquinolone moxifloxacin (MXF) and demonstrated its efficacy in treating Francisella tularensis infections both in vitro and in vivo. We compared two different nanovalve systems, positive and negative charge modifications of the mesopores, and different loading conditions鈥攙arying pH, cargo concentration, and duration of loading鈥揳nd identified conditions that maximize both the uptake and release capacity of MXF by MSNs. We have demonstrated in macrophage cell culture that the MSN-MXF delivery platform is highly effective in killing F. tularensis in infected macrophages, and in a mouse model of lethal pneumonic tularemia, we have shown that the drug-loaded MSNs are much more effective in killing F. tularensis than an equivalent amount of free MXF.