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: Article

66 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 originalEnglish
Páginas (desde-hasta)897-913
Número de páginas17
PublicaciónNanomedicine
Volumen5
N.º6
DOI
EstadoPublished - ago 2010

Huella dactilar

gold
Gold
peptide
Nanoparticles
Peptides
brain
Brain
Citric Acid
Liver
nanoparticle
Rats
Spleen
Mononuclear Phagocyte System
Neutrons
Pathology
pathology
Intraperitoneal Injections
Blood-Brain Barrier
Drug delivery
activation

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Bioengineering
  • Biomedical Engineering
  • Development
  • Materials Science(all)

Citar esto

Guerrero, S., Araya, E., Fiedler, J. L., Arias, J. I., Adura, C., Albericio, F., ... 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
Guerrero, Simon ; Araya, Eyleen ; Fiedler, Jenny L. ; Arias, J. Ignacio ; Adura, Carolina ; Albericio, Fernando ; Giralt, Ernest ; Arias, Jose Luis ; Fernndez, M. Soledad ; Kogan, Marcelo J. / Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide. En: Nanomedicine. 2010 ; Vol. 5, N.º 6. pp. 897-913.
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abstract = "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.",
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Guerrero, S, Araya, E, Fiedler, JL, Arias, JI, Adura, C, Albericio, F, Giralt, E, Arias, JL, Fernndez, MS & Kogan, MJ 2010, 'Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide', Nanomedicine, vol. 5, n.º 6, pp. 897-913. https://doi.org/10.2217/nnm.10.74

Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide. / Guerrero, Simon; Araya, Eyleen; Fiedler, Jenny L.; Arias, J. Ignacio; Adura, Carolina; Albericio, Fernando; Giralt, Ernest; Arias, Jose Luis; Fernndez, M. Soledad; Kogan, Marcelo J.

En: Nanomedicine, Vol. 5, N.º 6, 08.2010, p. 897-913.

Resultado de la investigación: Article

TY - JOUR

T1 - Improving the brain delivery of gold nanoparticles by conjugation with an amphipathic peptide

AU - Guerrero, Simon

AU - Araya, Eyleen

AU - Fiedler, Jenny L.

AU - Arias, J. Ignacio

AU - Adura, Carolina

AU - Albericio, Fernando

AU - Giralt, Ernest

AU - Arias, Jose Luis

AU - Fernndez, M. Soledad

AU - Kogan, Marcelo J.

PY - 2010/8

Y1 - 2010/8

N2 - 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.

AB - 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.

KW - Alzheimers disease

KW - amphipathic peptide

KW - bloodbrain barrier

KW - drug delivery

KW - nanobiomaterials

KW - nanotechnology

KW - neutron activation

KW - photothermal therapy

KW - targeting

KW - theranosis

KW - transcytosis

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DO - 10.2217/nnm.10.74

M3 - Article

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VL - 5

SP - 897

EP - 913

JO - Nanomedicine

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