Polymer functionalized gold nanoparticles as nonviral gene delivery reagents

Encabo-Berzosa, M.M. (Universidad de Zaragoza) ; Sancho-Albero, M. (Universidad de Zaragoza) ; Sebastian, V. (Universidad de Zaragoza) ; Irusta, S. (Universidad de Zaragoza) ; Arruebo, M. (Universidad de Zaragoza) ; Santamaria, J. (Universidad de Zaragoza) ; Martín Duque, P.

Resumen: Background: In the present study, we investigated the ability of polyethylene glycol (PEG) functionalized gold nanoparticles to function as nonviral vectors in the transfection of different cell lines, comparing them with commercial lipoplexes.

Methods: Positively-charged gold nanoparticles were synthesized using polyethylenimine (PEI) as a reducing and stabilizer agent and its cytotoxicity was reduced by its functionalization with PEG. We bound the nanoparticles to three plasmids with different sizes (4–40 kpb). Vector internalization was evaluated by confocal and electronic microscopy. Its transfection efficacy was studied by fluorescence microscopy and flow cytometry. The application of the resulting vector in gene therapy was evaluated indirectly using ganciclovir in HeLa cells transfected to express the herpes virus thymidine kinase.

Results: An appropriate ratio between the nitrogen from the PEI and the phosphorous from the phosphate groups of the DNA, together with a reduced size and an elevated electrokinetic potential, are responsible for an increased nanoparticle internalization and enhanced protein expression when carrying plasmids of up to 40 kbp (plasmid size close to the limit of the DNA-carrying capacity of viral vectors). Compared to a commercial transfection reagent, an equal or even higher expression of reporter genes (on HeLa and Hek293t) and a suicide effect on HeLa cells transfected with the herpes virus thymidine kinase gene were observed when using this novel nanoparticulated vector.

Conclusions: Nonviral vectors based on gold nanoparticles covalently coupled with PEG and PEI can be used as efficient transfection reagents showing expression levels that are the same or greater than those obtained with commercially available lipoplexes.

Idioma: Inglés

DOI: 10.1002/jgm.2964

Año: 2017

Publicado en: JOURNAL OF GENE MEDICINE 19, 6-7 (2017), e2964 [12 pp]
ISSN: 1099-498X

Factor impacto JCR: 1.647 (2017)

Categ. JCR: BIOTECHNOLOGY & APPLIED MICROBIOLOGY rank: 110 / 160 = 0.688 (2017) - Q3 - T3
Categ. JCR: MEDICINE, RESEARCH & EXPERIMENTAL rank: 101 / 133 = 0.759 (2017) - Q4 - T3
Categ. JCR: GENETICS & HEREDITY rank: 130 / 171 = 0.76 (2017) - Q4 - T3

Factor impacto SCIMAGO: 0.493 - Drug Discovery (Q3) - Molecular Medicine (Q3) - Molecular Biology (Q4) - Genetics (Q4) - Genetics (clinical) (Q4)

Financiación: info:eu-repo/grantAgreement/EC/FP7/614715/EU/A Photo-triggered On-demand Drug Delivery System for Chronic Pain/NANOHEDONISM

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Área Ingeniería Química (Dpto. Ing.Quím.Tecnol.Med.Amb.)