Engineered Filamentous Bacteriophages as Targeted Anti-bacterial Drug-carrying Nanomedicines
Lilach Vaks and Itai Benhar
from: Phage Therapy: Current Research and Applications (Edited by: Jan Borysowski, Ryszard Międzybrodzki and Andrzej Górski). Caister Academic Press, U.K. (2014)
The increasing development of bacterial resistance to traditional antibiotics forces the scientists to develop new antimicrobial approaches. In traditional as well as newly developed antibiotics, the drug itself provides the target specificity, thus excluding potent but non-selective drugs from possible use. The conjugation of a toxic drug to a targeted carrier replaces the drug selectivity by the targeting moiety of the carrier thus maximizing the drug bio-availability to diseased tissues and minimizing the healthy tissues exposure. Bacteriophages (phages) possess unique characteristics such as modular nanometric structure, high specificity to host bacteria, an ability to display foreign proteins on the phage surface and varying levels of tolerance to chemical modification which suggest they may be perfect carriers for targeting and eradication of bacterial pathogens. The natural ability of host-specific phages to infect and lyse their host bacteria in animal disease models was already demonstrated in early 1940s. However, major challenges such as limited host specificity, uncontrolled replication and high immunogenicity remained mostly unaddressed. The application of phage carriers loaded with non-selective antibacterial drugs provides for drug accumulation at high concentration vicinal to the target pathogen and its effective killing with minimal effect on the organism infected by the pathogen. The targeting moiety is provided by either natural host-specific recognition or by genetic modification of the phage to display pathogen-specific peptide or antibody on phage surface. Such approaches were demonstrated mostly with filamentous phages, but also with tailed phages. The drug conjugation affects the phage in vivo properties and decreases its immunogenicity. In conclusion, the unique natural properties of the phage carrier and its universal compatibility for drug conjugation and for display of target-specific proteins and peptides give the phage nanoparticle an exclusive advantage among the presently existing anti bacterial drug-delivery systems read more ...