title: Effectiveness, against tuberculosis, of pseudo-ternary complexes: peptide-DNA-cationic liposome.
abstract: We report the effects of a synthetic peptide designed to act as a nuclear localization signal on the treatment of tuberculosis. The peptide contains 21 amino acid residues with the following specific domains: nuclear localization signal from SV 40T, cationic shuttle sequence, and cysteamide group at the C-terminus. The peptide was complexed with the plasmid DNAhsp65 and incorporated into cationic liposomes, forming a pseudo-ternary complex. The same cationic liposomes, composed of egg chicken L-α-phosphatidylcholine, 1,2-dioleoyl-3-trimethylammonium-propane, and 1,2-dioleoyl-3-trimethylammonium-propane (2:1:1M), were previously evaluated as a gene carrier for tuberculosis immunization protocols with DNAhsp65. The pseudo-ternary complex presented a controlled size (250 nm), spherical-like shape, and various lamellae in liposomes as evaluated by transmission electron microscopy. An assay of fluorescence probe accessibility confirmed insertion of the peptide/DNA into the liposome structure. Peptide addition conferred no cytotoxicity in vitro, and similar therapeutic effects against tuberculosis were seen with four times less DNA compared with naked DNA treatment. Taken together, the results indicate that the pseudo-ternary complex is a promising gene vaccine for tuberculosis treatment. This work contributes to the development of multifunctional nanostructures in the search for strategies for in vivo DNA delivery.
authors: Núcleo de Pesquisas em Tuberculose, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, São Paulo, SP, Brazil.
authors: Rogério Silva
authors: RS
authors: Rosada
authors: Célio Lopes
authors: CL
authors: Silva
authors: Maria Helena Andrade
authors: MH
authors: Santana
authors: Clóvis Ryuichi
authors: CR
authors: Nakaie
authors: Lucimara Gaziola
authors: LG
authors: de la Torre
mesh_terms: D000818:Animals; D002412:Cations / Q000737:chemistry / Q000627:therapeutic use; D004247:DNA / Q000737:chemistry / Q000627:therapeutic use*; D015316:Genetic Therapy; D008081:Liposomes / Q000737:chemistry / Q000627:therapeutic use*; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000302:isolation & purification; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry / Q000627:therapeutic use*; D014376:Tuberculosis / Q000188:drug therapy*
chemical_list: D002412:Cations; D008081:Liposomes; D010455:Peptides; D004247:DNA