Improving The Brain Delivery of Gold Nanoparticles by Conjugation with An Amphipathic Peptide

Abstract

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.

Effect of surface coating on the biodistribution profile of gold nanoparticles in the rat

“…egy to improve brain delivery in the rat [23]. Regarding the peptide-functionalized AuNPs employed in our study, the general trend of distribution did not differ from the one described for Cit-AuNPs; however, increased Au levels in the liver were attained for CALNN-, CALNS-and CALND-capped AuNPs at 24 h post-injection, with values significantly higher than those found for Cit-AuNPs.…”

“…Nevertheless, liver and spleen remained the preferential sites of the accumulation of the PEG-AuNPs. Recently, a study by Guerrero et al [23] demonstrated that conjugation of the amphipathic peptide CLPFFD to the AuNP surface increased in vivo brain delivery, while simultaneously reducing its retention in the spleen 1 and 2 h after intraperitoneal (i.p.) injection in the rat, as compared with citrate-coated AuNPs of the same size.…”

Peptides and proteins used to enhance gold nanoparticle delivery to the brain: preclinical approaches

“…110,111 This peptide is a β-breaker peptide designed by Soto et al 112 (which is based on the original sequence of β-amyloid), and contains a Cys added to the extreme N-terminal portion of the peptide for the chemisorption to the gold surface resulting in the conjugate AuNP-CLPFFD. This conjugate is used for the microwave destruction of β-amyloid toxic aggregates.…”

“…65 However, in other studies, we determined in vitro that GNSs and GNRs functionalized with the peptide CLPFFD did not produce effects on the cell viability of neurons. 2,110 A very relevant point is that to determine the potential neurotoxic effect of nanoparticles, it is necessary to increase the local concentration in the brain.…”

“…125 An important aspect to consider is that the structure of the peptide anchored to the nanoparticle should not be changed after it is attached to the surface of the nanoparticles when the delivery strategy involves the recognition of a receptor, as discussed in previous works. 3,110,115,126 Using different techniques is relevant to determine the structure of the ligand on the AuNP surface and the number of peptides per nanoparticle, which is relevant for the interaction with the target. Various techniques have been employed for such purposes such as circular dichroism -which provides information about the secondary structure of the peptide, 127 nuclear magnetic resonance -which provides information related to the structure of the molecules, 128 infrared spectroscopy -which is used in the presence of functional groups 129 on the surface, and surface-enhanced Raman spectroscopy.…”