Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor

Prades, Roger; Guerrero, Simón; Araya, Eyleen; Molina, Carlos; Salas, Edison; Zurita, Esther; Selva, Javier; Egea, Gustavo; López‐Iglesias, Carmen; Teixidó, Meritxell; Kogan, Marcelo J.; Giralt, Ernest

doi:10.1016/j.biomaterials.2012.06.063

Cited by 236 publications

(183 citation statements)

References 39 publications

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“…In general, high transport rates have been demonstrated to be expected mainly in BBB models with lower permeability property37 as well as for nanosystems employing specific brain‐targeting ligands 38. However, for DSA the percentage of transport is higher compared to published rates of gold‐NP (conjugated to therapeutic agent and brain‐targeted peptide), transferrin receptor‐targeted immunoliposomes and neutral, anionic, and cationic malto‐dextrin 60 nm nanoparticles showing a percentage of transport which varies from 0.4% to 14% 39. Thus, the high in vitro transport efficiency for DSA shows very promising brain‐targeting properties of the investigated PAMAM dendrimer bioconjugates.…”

Section: Resultsmentioning

confidence: 99%

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Moscariello

Jansen

et al. 2018

Advanced Science

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Neurological disorders are undoubtedly among the most alarming diseases humans might face. In treatment of neurological disorders, the blood‐brain barrier (BBB) is a challenging obstacle preventing drug penetration into the brain. Advances in dendrimer chemistry for central nervous system (CNS) treatments are presented here. A poly(amido)amine (PAMAM) dendrimer bioconjugate with a streptavidin adapter for the attachment of dendrons or any biotinylated drug is constructed. In vitro studies on porcine or murine models and in vivo mouse studies are performed and reveal the permeation of dendronized streptavidin (DSA) into the CNS. The bioconjugate is taken up mainly by the caveolae pathway and transported across the BBB via transcytosis escaping from lysosomes. After transcytosis DSA are delivered to astrocytes and neurons. Furthermore, DSA offer high biocompatibility in vitro and in vivo. In summary, a new strategy for implementing therapeutic PAMAM function as well as drug delivery in neuropathology is presented here.

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Section: Resultsmentioning

confidence: 99%

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Moscariello

Jansen

et al. 2018

Advanced Science

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“…Peptides were loaded onto C 18 Zorbax precolumn (Agilent Technologies, cat #5065-9913) and separated by reversephase chromatography using a 12-cm column with an inner diameter of 75 µm, packed with 5 µm C 18 particles (Nikkyo Technos Co., Ltd. Japan).…”

Section: Ltq-orbitrap-xlmentioning

confidence: 99%

Chemically synthesized peptide libraries as a new source of BBB shuttles. Use of mass spectrometry for peptide identification

Guixer

Arroyo

Belda³

et al. 2016

Journal of Peptide Science

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ABSTRACT:The blood-brain barrier (BBB) is a biological barrier that protects the brain from neurotoxic agents and regulates the influx and efflux of molecules required for its correct function. This stringent regulation hampers the passage of brain parenchyma-targeting drugs across the BBB. BBB shuttles have been proposed as a way to overcome this hurdle since these peptides can not only cross the BBB but also carry molecules which would otherwise be unable to cross the barrier unaided.Here we developed a new high-throughput screening methodology to identify new peptide BBB shuttles in a broadly unexplored chemical space. By introducing D-amino acids, this approach screens only protease-resistant peptides. This methodology combines combinatorial chemistry for peptide library synthesis, in vitro models mimicking the BBB for library evaluation, and state-of-the-art mass spectrometry techniques to identify those peptides able to cross the in vitro assays. BBB shuttle synthesis was performed by the mix-andsplit technique to generate a library based on the following: Ac-D-Arg-XXXXX-NH 2 , where X were: D-Ala (a), D-Arg (r), D-Ile (i), D-Glu (e), D-Ser (s), D-Trp (w), or D-Pro (p). The assays used comprised the in vitro cell-based BBB assay (mimicking both active and passive transport) and the PAMPA (mimicking only passive diffusion). The identification of candidates was determined using a twostep mass spectrometry approach combining LTQ-Orbitrap and Q-trap mass spectrometers.Identified sequences were postulated to cross the BBB models. We hypothesized that some sequences cross the BBB through passive diffusion mechanisms and others through other mechanisms, including paracellular flux and active transport.These results provide a new set of BBB shuttle peptide families. Furthermore, the methodology described is proposed as a consistent approach to search for protease-resistant therapeutic peptides. KEYWORDS:Blood-brain barrier (BBB), mass spectrometry (MS), LTQ-Orbitrap, Q-trap, single reaction monitoring (SRM), in vitro cell-based BBB model, parallel artificial membrane permeability assay (PAMPA), mix-and-split, solid-phase peptide synthesis (SPPS).

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“…We assume that the presence of RDP on the nanoparticle surfaces is what promoted the cellular transport, which is consistent with a previous report. 32 To further identify the cell specificity of the RDP-AuNCs, one type of non-neuronal cell, human lung A549, was used to compare the internalization efficacy with that of a neural cell, SH-SY5Y. The results showed that the fluorescence intensity of RDP-AuNCs-treated A549 cells was far lower than that of RDP-AuNCs-treated SH-SY5Y ( Figure 2B).…”

Section: Rdp-auncs Specifically Enter the Neural Cellsmentioning

confidence: 99%

A new strategy for specific imaging of neural cells based on peptide-conjugated gold nanoclusters

Zhang

2015

IJN

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Despite the significant progress in molecular imaging technologies that has been made in recent years, the specific detection of neural cells still remains challenging. Here, we suggest the use of gold nanoclusters (AuNCs) modified with a brain-targeting peptide as a potential imaging candidate for detecting neural cells in vitro and in mice. AuNCs of less than 10 nm (dynamic light scattering analysis) were first prepared using the “green” synthetic approach, and then a targeting peptide, rabies virus glycoprotein derived peptide (RDP), was conjugated to the AuNCs for improving the efficiency and specificity of neural cell penetration. The conjugate’s mechanism of cellular attachment and entry into neural cells was suggested to be receptor-mediated endocytosis through clathrin-coated pits. Also, noninvasive imaging analysis and animal studies indicated that the RDP-modified nanoclusters could concentrate in the brain and locate in neural cells. This study suggests the feasibility of using targeting peptide-modified nanoclusters for noninvasive imaging brain cells in vivo.

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Delivery of gold nanoparticles to the brain by conjugation with a peptide that recognizes the transferrin receptor

Cited by 236 publications

References 39 publications

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Brain Delivery of Multifunctional Dendrimer Protein Bioconjugates

Chemically synthesized peptide libraries as a new source of BBB shuttles. Use of mass spectrometry for peptide identification

A new strategy for specific imaging of neural cells based on peptide-conjugated gold nanoclusters

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