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Nanoparticle mediated delivery of pure P53 supercoiled plasmid DNA for gene therapy.
Gaspar, Vítor M; Correia, Ilídio J; Sousa, Angela; Silva, Filomena; Paquete, Catarina M; Queiroz, João A; Sousa, Fani.
Afiliación
  • Gaspar VM; CICS-UBI-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interior, Covilhã, Portugal.
J Control Release ; 156(2): 212-22, 2011 Dec 10.
Article en En | MEDLINE | ID: mdl-21864596
The translation of non-viral gene replacement therapies for cancer into clinical application is currently hindered due to known issues associated with the effectiveness of plasmid DNA (pDNA) expression vectors and the production of gene delivery vehicles. Herein we report an integrative approach established on the synthesis of nanoparticulated carriers, in association with the supercoiled (sc) isoform purification of a p53 tumor suppressor encoding plasmid, to improve both delivery and transfection. An arginine-based chromatographic matrix with specific recognition for the different topoisoforms was used to completely isolate the biologically active sc pDNA. Our findings showed that the sc topoisoform is recovered under mild conditions with high purity and structural stability. In addition, to further enhance protection and transfection efficiency, the naked sc pDNA was encapsulated within chitosan nanoparticles by ionotropic gelation. The mild conditions for particle synthesis used in the former technique allowed the attainment of a high encapsulation efficiency for sc pDNA (>75%). Moreover, in vitro transfection experiments confirmed the reinstatement of the p53 protein expression and most importantly, the sc pDNA transfected cells exhibited the highest p53 expression levels when compared to other formulations. Overall, given the fact that sc pDNA topoisoform indeed enhances transgene expression rates this approach might have a profound impact on the development of a sustained nucleic acid-based therapy for cancer.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plásmidos / ADN Superhelicoidal / Transfección / Proteína p53 Supresora de Tumor / Nanopartículas / Neoplasias Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Países Bajos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Plásmidos / ADN Superhelicoidal / Transfección / Proteína p53 Supresora de Tumor / Nanopartículas / Neoplasias Límite: Animals / Humans Idioma: En Revista: J Control Release Asunto de la revista: FARMACOLOGIA Año: 2011 Tipo del documento: Article País de afiliación: Portugal Pais de publicación: Países Bajos