The highly efficient elimination of intracellular bacteria via a metal organic framework (MOF)-based three-in-one delivery system.

Abstract

Numerous infectious diseases that cause clinical failures and relapses after antibiotic therapy have been confirmed to be induced by pathogenic intracellular bacteria. The existing therapeutic strategies fail to eliminate intracellular bacteria mainly due to a guard reservoir provided by the cell membrane, which can deactivate antibiotics. Herein, we have reported the design of a pH-responsive metal organic framework (MOF)/antibiotic synergistic system for the targeted highly efficient elimination of intracellular bacteria. The obtained tetracycline (Tet)@ZIF-8@ hyaluronic acid (HA) system (abbreviated to TZH) can be taken up by cells owing to the presence of CD44 receptors on the cell surface via an HA-mediated pathway. Zinc ions and antibiotics, released from TZH under acidic conditions caused by bacteria, have a synergistic antibacterial effect both in vitro and in vivo. The clearance rate of TZH to the intracellular bacteria reached over 98% within the limits of biotoxicity, which indicated that this delivery system can pass the cell membrane "barriers" and restore the efficacy of endangered antibiotics. This synergistic strategy shows potential in optimizing the efficacy-dosage correlation of antibiotics for related infection treatments and constructing versatile controlled release delivery systems for a broad range of applications.

• Authors: Xu Zhang , Lizhi Liu , Lunjie Huang , Wentao Zhang , Rong Wang , Tianli Yue , Jing Sun , Guoliang Li , Jianlong Wang
• Journal: Nanoscale (Nanoscale) Vol. 11 Issue 19 Pg. 9468-9477 (May 16 2019) ISSN: 2040-3372 [Electronic] England
• PMID: 31044197 (Publication Type: Journal Article)

Chemical References

• Anti-Bacterial Agents
• Drug Carriers
• Metal-Organic Frameworks
• Hyaluronic Acid
• Tetracycline

Topics

• Animals
• Anti-Bacterial Agents (chemistry, metabolism, pharmacology, therapeutic use)
• Bacteria (drug effects)
• Bacterial Infections (drug therapy, pathology)
• Drug Carriers (chemistry)
• Drug Liberation
• Hyaluronic Acid (chemistry)
• Hydrogen-Ion Concentration
• Metal-Organic Frameworks (chemistry)
• Mice
• Salmonella (drug effects)
• Staphylococcus aureus (drug effects)
• Tetracycline (chemistry, metabolism, pharmacology, therapeutic use)