title: Bacteria-Targeting Conjugates Based on Antimicrobial Peptide for Bacteria Diagnosis and Therapy.
abstract: Chloramphenicol (CAP) is one of the most effective antimicrobial agents, but its therapeutic efficacy is greatly limited by its nonspecific distribution and consequent side effects in neutrophils. Targeting to the infection sites, and thus restricting CAP nonselective delivery, provides an alternative way to overcome this limitation. The antibacterial peptide fragment UBI29-41 was identified to have a high bacterial affinity. However, no research so far has been carried out to utilize UBI29-41 as a ligand for bacteria-targeting therapies. In this Article, we first labeled a near-infrared fluorescent dye (ICG02) with UBI29-41 to investigate its targeting capability in different bacteria (S. aureus, E. coli, and P. auruginosa) and bacteria-infected mouse models. Subsequently, UBI29-41 was conjugated with the typical antibiotic (CAP) through the linker glutaric anhydride to form the conjugate CAP-UBI29-41 for the bacteria-targeting therapy. In vitro studies demonstrated the enhanced antibacterial effects of CAP-UBI29-41 on S. aureus and E.coil. Meanwhile, the toxicity of CAP-UBI29-41 on normal cells decreased distinctly in comparison with CAP. Most importantly, CAP-UBI29-41 exhibited more favorable antibacterial efficacy than CAP in bacteria-bearing mouse models. All these results demonstrated that UBI29-41 is an ideal targeting ligand to construct antibacterial agents for bacteria-targeting therapy.
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Haiyan
authors.initials: H
authors.lastname: Chen
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Cuicui
authors.initials: C
authors.lastname: Liu
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Chen
authors.affiliation: §Department of Chemistry, University of California, 900 University Avenue, Riverside, California 92521, United States.
authors.forename: Kyle
authors.initials: K
authors.lastname: Madrid
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Shuwen
authors.initials: S
authors.lastname: Peng
authors.forename: Xinyue
authors.initials: X
authors.lastname: Dong
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Min
authors.initials: M
authors.lastname: Zhang
authors.affiliation: †Department of Biomedical Engineering, School of Engineering, State Key Laboratory of Natural Medicines, and ‡School of Pharmacy, China Pharmaceutical University, 24 Tongjia Lane, Gulou District, Nanjing 210009, China.
authors.forename: Yueqing
authors.initials: Y
authors.lastname: Gu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001424:Bacterial Infections / Q000188:drug therapy*; D002460:Cell Line; D002701:Chloramphenicol / Q000494:pharmacology; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D010446:Peptide Fragments / Q000494:pharmacology*; D019265:Spectroscopy, Near-Infrared / Q000379:methods
chemical_list: D000900:Anti-Bacterial Agents; D010446:Peptide Fragments; D002701:Chloramphenicol
keywords: UBI29−41; bacteria-targeting; chloramphenicol; diagnosis; therapy