TY - JOUR
T1 - Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor
AU - Prades, Roger
AU - Guerrero, Simón
AU - Araya, Eyleen
AU - Molina, Claudia
AU - Salas, Edison
AU - Zurita, Esther
AU - Selva, Javier
AU - Egea, Gustavo
AU - López-Iglesias, Carmen
AU - Teixidó, Meritxell
AU - Kogan, Marcelo J.
AU - Giralt, Ernest
N1 - Funding Information:
We thank Prof. M. Garcia from the University of Barcelona and I. Martín from the Institute for Research in Biomedicine (IRB Barcelona) for performing the zeta potential measurements, J. Calderón from the Agència de Salut Pública de Barcelona for technical support in the ICP-MS measurements, and S. Madurga from the University of Barcelona for the in silico calculations. This study was supported by AECID , Fondecyt 1090143, ANILLO ACT-95, CONSOLIDER-INGENIO 2010, the Generalitat de Catalunya (XRB and 2009SGR-1005 ), MECESUP-UCH-0811 and BFU 2009-07186.
PY - 2012/10
Y1 - 2012/10
N2 - The treatment of Alzheimer's disease and many other brain-related disorders is limited because of the presence of the blood-brain barrier, which highly regulate the crossing of drugs. Metal nanoparticles have unique features that could contribute to the development of new therapies for these diseases. Nanoparticles have the capacity to carry several molecules of a drug; furthermore, their unique physico-chemical properties allow, for example, photothermal therapy to produce molecular surgery to destroy tumor cells and toxic structures. Recently, we demonstrated that gold nanoparticles conjugated to the peptide CLPFFD are useful to destroy the toxic aggregates of β-amyloid, similar to the ones found in the brains of patients with Alzheimer's disease. However, nanoparticles, like many other compounds, have null or very low capacity to cross the blood-brain barrier. In order to devise a strategy to improve drug delivery to the brain, here we introduced the peptide sequence THRPPMWSPVWP into the gold nanoparticle-CLPFFD conjugate. This peptide sequence interacts with the transferrin receptor present in the microvascular endothelial cells of the blood-brain barrier, thus causing an increase in the permeability of the conjugate in brain, as shown by experiments in vitro and in vivo. Our results are highly relevant for the therapeutic applications of gold nanoparticles for molecular surgery in the treatment of neurodegenerative diseases such as Alzheimer's disease.
AB - The treatment of Alzheimer's disease and many other brain-related disorders is limited because of the presence of the blood-brain barrier, which highly regulate the crossing of drugs. Metal nanoparticles have unique features that could contribute to the development of new therapies for these diseases. Nanoparticles have the capacity to carry several molecules of a drug; furthermore, their unique physico-chemical properties allow, for example, photothermal therapy to produce molecular surgery to destroy tumor cells and toxic structures. Recently, we demonstrated that gold nanoparticles conjugated to the peptide CLPFFD are useful to destroy the toxic aggregates of β-amyloid, similar to the ones found in the brains of patients with Alzheimer's disease. However, nanoparticles, like many other compounds, have null or very low capacity to cross the blood-brain barrier. In order to devise a strategy to improve drug delivery to the brain, here we introduced the peptide sequence THRPPMWSPVWP into the gold nanoparticle-CLPFFD conjugate. This peptide sequence interacts with the transferrin receptor present in the microvascular endothelial cells of the blood-brain barrier, thus causing an increase in the permeability of the conjugate in brain, as shown by experiments in vitro and in vivo. Our results are highly relevant for the therapeutic applications of gold nanoparticles for molecular surgery in the treatment of neurodegenerative diseases such as Alzheimer's disease.
KW - Alzheimer's disease
KW - Blood-brain barrier
KW - Blood-brain barrier shuttle
KW - Gold nanoparticles
KW - Molecular surgery
KW - Transferrin receptor
UR - http://www.scopus.com/inward/record.url?scp=84864313094&partnerID=8YFLogxK
U2 - 10.1016/j.biomaterials.2012.06.063
DO - 10.1016/j.biomaterials.2012.06.063
M3 - Article
C2 - 22795856
AN - SCOPUS:84864313094
SN - 0142-9612
VL - 33
SP - 7194
EP - 7205
JO - Biomaterials
JF - Biomaterials
IS - 29
ER -