1. Tandem Guest‐Host‐Receptor Recognitions Precisely Guide Ciprofloxacin to Eliminate Intracellular Staphylococcus aureus.
- Author
-
Zhan, Wenjun, Xu, Lingling, Liu, Zhiyu, Liu, Xiaoyang, Gao, Ge, Xia, Tiantian, Cheng, Xiaotong, Sun, Xianbao, Wu, Fu‐Gen, Yu, Qian, and Liang, Gaolin
- Subjects
- *
CIPROFLOXACIN , *NANOPARTICLES , *CASPASES , *ADAMANTANE , *TREATMENT effectiveness , *MANNOSE - Abstract
Staphylococcus aureus (S. aureus) is able to hide within host cells to escape immune clearance and antibiotic action, causing life‐threatening infections. To boost the therapeutic efficacy of antibiotics, new intracellular delivery approaches are urgently needed. Herein, by rational design of an adamantane (Ada)‐containing antibiotic‐peptide precursor Ada‐Gly‐Tyr‐Val‐Ala‐Asp‐Cys(StBu)‐Lys(Ciprofloxacin)‐CBT (Cip‐CBT‐Ada), we propose a strategy of tandem guest‐host‐receptor recognitions to precisely guide ciprofloxacin to eliminate intracellular S. aureus. Via guest‐host recognition, Cip‐CBT‐Ada is decorated with a β‐cyclodextrin‐heptamannoside (CD‐M) derivative to yield Cip‐CBT‐Ada/CD‐M, which is able to target mannose receptor‐overexpressing macrophages via multivalent ligand‐receptor recognition. After uptake, Cip‐CBT‐Ada/CD‐M undergoes caspase‐1 (an overexpressed enzyme during S. aureus infection)‐initiated CBT‐Cys click reaction to self‐assemble into ciprofloxacin nanoparticle Nano‐Cip. In vitro and in vivo experiments demonstrate that, compared with ciprofloxacin or Cip‐CBT‐Ada, Cip‐CBT‐Ada/CD‐M shows superior intracellular bacteria elimination and inflammation alleviation efficiency in S. aureus‐infected RAW264.7 cells and mouse infection models, respectively. This work provides a supramolecular platform of tandem guest‐host‐receptor recognitions to precisely guide antibiotics to eliminate intracellular S. aureus infection efficiently. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF