title: An isoniazid analogue promotes Mycobacterium tuberculosis-nanoparticle interactions and enhances bacterial killing by macrophages.
abstract: Nanoenabled drug delivery systems against tuberculosis (TB) are thought to control pathogen replication by targeting antibiotics to infected tissues and phagocytes. However, whether nanoparticle (NP)-based carriers directly interact with Mycobacterium tuberculosis and how such drug delivery systems induce intracellular bacterial killing by macrophages is not defined. In the present study, we demonstrated that a highly hydrophobic citral-derived isoniazid analogue, termed JVA, significantly increases nanoencapsulation and inhibits M. tuberculosis growth by enhancing intracellular drug bioavailability. Importantly, confocal and atomic force microscopy analyses revealed that JVA-NPs associate with both intracellular M. tuberculosis and cell-free bacteria, indicating that NPs directly interact with the bacterium. Taken together, these data reveal a nanotechnology-based strategy that promotes antibiotic targeting into replicating extra- and intracellular mycobacteria, which could actively enhance chemotherapy during active TB.
authors.affiliation: Laboratory of Immunobiology, Department of Microbiology, Immunology and Parasitology, Universidade Federal de Santa Catarina, Florianopolis, Brazil.
authors.forename: Tatiany J
authors.initials: TJ
authors.lastname: de Faria
authors.forename: Mariane
authors.initials: M
authors.lastname: Roman
authors.forename: Nicole M
authors.initials: NM
authors.lastname: de Souza
authors.forename: Rodrigo
authors.initials: R
authors.lastname: De Vecchi
authors.forename: João Vitor
authors.initials: JV
authors.lastname: de Assis
authors.forename: Ana Lúcia Gomes
authors.initials: AL
authors.lastname: dos Santos
authors.forename: Ivan H
authors.initials: IH
authors.lastname: Bechtold
authors.forename: Nathalie
authors.initials: N
authors.lastname: Winter
authors.forename: Maurilio José
authors.initials: MJ
authors.lastname: Soares
authors.forename: Luciano Paulino
authors.initials: LP
authors.lastname: Silva
authors.forename: Mauro V
authors.initials: MV
authors.lastname: De Almeida
authors.forename: André
authors.initials: A
authors.lastname: Báfica
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D001682:Biological Availability; D002478:Cells, Cultured; D004339:Drug Compounding; D016503:Drug Delivery Systems / Q000379:methods; D006863:Hydrogen-Ion Concentration; D057927:Hydrophobic and Hydrophilic Interactions; D007538:Isoniazid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D019344:Lactic Acid / Q000737:chemistry; D008264:Macrophages / Q000187:drug effects* / Q000382:microbiology; D051379:Mice; D018625:Microscopy, Atomic Force; D018613:Microscopy, Confocal; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000502:physiology; D053758:Nanoparticles; D010316:Particle Size; D010587:Phagocytosis; D011100:Polyglycolic Acid / Q000737:chemistry; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D000077182:Polylactic Acid-Polyglycolic Acid Copolymer; D011100:Polyglycolic Acid; D019344:Lactic Acid; D007538:Isoniazid