title: Tetracycline nanoparticles as antibacterial and gene-silencing agents.
abstract: The spread of antibiotic-resistant bacteria and parasites calls for the development of new therapeutic strategies with could potentially reverse this trend. Here, a proposal is presented to exploit a sonochemical method to restore the antibiotic activity of tetracycline (TTCL) against resistant bacteria by converting the antibiotic into a nanoparticulate form. The demonstrated sonochemical method allows nanoscale TTCL assembly to be driven by supramolecular hydrogen bond formation, with no further modification to the antibiotic's chemical structure. It is shown that tetracycline nanoparticles (TTCL NPs) can act as antibacterial agents, both against TTCL sensitive and against resistant bacterial strains. Moreover, the synthesized antibiotic nanoparticles (NPs) can act as effective gene-silencing agents through the use of a TTCL repressor in Trypanosome brucei parasites. It is demonstrated that the NPs are nontoxic to human cells and T. brucei parasites and are able to release their monomer components in an active form in a manner that results in enhanced antimicrobial activity relative to a homogeneous solution of the precursor monomer. As the TTCL NPs are biocompatible and biodegradable, sonochemical formation of TTCL NPs represents a new promising approach for generation of pharmaceutically active nanomaterials.
authors.affiliation: Department of Chemistry, University of Cambridge, Lensfield road, Cambridge, CB2 1EW, UK.
authors.forename: Ulyana
authors.initials: U
authors.lastname: Shimanovich
authors.forename: Anat
authors.initials: A
authors.lastname: Lipovsky
authors.forename: Dror
authors.initials: D
authors.lastname: Eliaz
authors.forename: Sally
authors.initials: S
authors.lastname: Zigdon
authors.forename: Tuomas P J
authors.initials: TP
authors.lastname: Knowles
authors.forename: Yeshayahu
authors.initials: Y
authors.lastname: Nitzan
authors.forename: Shulamit
authors.initials: S
authors.lastname: Michaeli
authors.forename: Aharon
authors.initials: A
authors.lastname: Gedanken
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology; D002460:Cell Line; D020868:Gene Silencing / Q000187:drug effects*; D006801:Humans; D050296:Microbial Viability / Q000187:drug effects; D053758:Nanoparticles / Q000737:chemistry*; D013752:Tetracycline / Q000737:chemistry* / Q000494:pharmacology; D014346:Trypanosoma brucei brucei / Q000187:drug effects / Q000235:genetics / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D013752:Tetracycline
keywords: antibiotics; nanoparticles; resistant bacteria; sonochemistry