Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide

Simon Guerrero, Eyleen Araya, Jenny L. Fiedler, J. Ignacio Arias, Carolina Adura, Fernando Albericio, Ernest Giralt, Jose Luis Arias, M. Soledad Fernndez, Marcelo J. Kogan

Resultado de la investigación: Contribución a una revistaArtículo

71 Citas (Scopus)

Resumen

Background & Aims: Gold nanoparticles (GNPs) have promising applications for drug delivery as well as for the diagnosis and treatment of several pathologies, such as those related to the CNS. However, GNPs are retained in a number of organs, such as the liver and spleen. Owing to their negative charge and/or processes of opsonization, GNPs are retained by the reticuloendothelial system, thereby decreasing their delivery to the brain. It is therefore crucial to modify the nanoparticle surface in order to increase its lipophilicity and reduce its negative charge, thus achieving enhanced delivery to the brain. Results: In this article, we have shown that conjugation of 12 nm GNPs with the amphipathic peptide CLPFFD increases the in vivo penetration of these particles to the rat brain. The C(GNP)-LPFFD conjugates showed a smaller negative charge and a greater hydrophobic character than citrate-capped GNPs of the same size. We administered intraperitoneal injections of citrate GNPs and C(GNP)-LPFFD in rats, and determined the gold content in the tissues by neutron activation. Compared with citrate GNPs, the C(GNP)-LPFFD conjugate improved the delivery to the brain, increasing the concentration of gold by fourfold, while simultaneously reducing its retention by the spleen 1 and 2 h after injection. At 24 h, the conjugate was partially cleared from the brain, and mainly accumulated in the liver. The C(GNP)-LPFFD did not alter the integrity of the blood-brain barrier, and had no effect on cell viability.

Idioma originalInglés
Páginas (desde-hasta)897-913
Número de páginas17
PublicaciónNanomedicine
Volumen5
N.º6
DOI
EstadoPublicada - ago 2010

Áreas temáticas de ASJC Scopus

  • Medicina (miscelánea)
  • Bioingeniería
  • Ingeniería biomédica
  • Desarrollo
  • Ciencia de los materiales (todo)

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    Guerrero, S., Araya, E., Fiedler, J. L., Arias, J. I., Adura, C., Albericio, F., Giralt, E., Arias, J. L., Fernndez, M. S., & Kogan, M. J. (2010). Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide. Nanomedicine, 5(6), 897-913. https://doi.org/10.2217/nnm.10.74