title: Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide.
abstract: OBJECTIVE
  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.
authors.affiliation: Facultad de Ciencias Químicas y Farmaceúticas, Universidad de Chile, Santiago, Chile.
authors.forename: Simon
authors.initials: S
authors.lastname: Guerrero
authors.forename: Eyleen
authors.initials: E
authors.lastname: Araya
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Fiedler
authors.forename: J Ignacio
authors.initials: JI
authors.lastname: Arias
authors.forename: Carolina
authors.initials: C
authors.lastname: Adura
authors.forename: Fernando
authors.initials: F
authors.lastname: Albericio
authors.forename: Ernest
authors.initials: E
authors.lastname: Giralt
authors.forename: Jose Luis
authors.initials: JL
authors.lastname: Arias
authors.forename: M Soledad
authors.initials: MS
authors.lastname: Fernández
authors.forename: Marcelo J
authors.initials: MJ
authors.lastname: Kogan
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism*; D006046:Gold; D053768:Metal Nanoparticles; D010455:Peptides / Q000737:chemistry*; D051381:Rats
chemical_list: D010455:Peptides; D006046:Gold