This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Reprints and Permissions Copyright Information Books from ASM Press MicrobeWorld Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Yacoby, I. Articles by Benhar, I. Search for Related Content PubMed PubMed Citation Articles by Yacoby, I. Articles by Benhar, I. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Antibiotics Hazardous Substances DB CHLORAMPHENICOL NEOMYCIN

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, June 2007, p. 2156-2163, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.00163-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines

Iftach Yacoby, Hagit Bar, and Itai Benhar^*

Department of Molecular Microbiology and Biotechnology, The George S. Wise Faculty of Life Sciences, Tel-Aviv University, Ramat Aviv 69978, Israel

Received 5 February 2007/ Returned for modification 15 March 2007/ Accepted 19 March 2007

While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of 20,000 compared to the free drug.

---

* Corresponding author. Mailing address: Green Building Room 202, Department of Molecular Microbiology and Biotechnology, Tel-Aviv University, Ramat Aviv 69978, Israel. Phone: 972 3 6407511. Fax: 972 3 6409407. E-mail: benhar{at}post.tau.ac.il

Published ahead of print on 2 April 2007.

---

Antimicrobial Agents and Chemotherapy, June 2007, p. 2156-2163, Vol. 51, No. 6
0066-4804/07/$08.00+0     doi:10.1128/AAC.00163-07
Copyright © 2007, American Society for Microbiology. All Rights Reserved.

This article has been cited by other articles:

• Kuzmicheva, G.A., Jayanna, P.K., Eroshkin, A.M., Grishina, M.A., Pereyaslavskaya, E.S., Potemkin, V.A., Petrenko, V.A. (2009). Mutations in fd phage major coat protein modulate affinity of the displayed peptide. Protein Eng Des Sel 22: 631-639 [Abstract] [Full Text]