Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer’s Disease

Droumaguet, Benjamin Le; Nicolas, Julien; Brambilla, Davide; Mura, Simona; Maksimenko, Andrei; Kimpe, Line De; Salvati, Elisa; Zona, Cristiano; Airoldi, Cristina; Canovi, Mara; Gobbi, Marco; Noiray, Magali; Ferla, Barbara La; Nicotra, Francesco; Scheper, Wiep; Flores, Orfeu; Masserini, Massimo; Andrieux, Karine; Couvreur, Patrick

doi:10.1021/nn3004372

Cited by 130 publications

(119 citation statements)

References 54 publications

(85 reference statements)

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“…The coupling of Curc molecules to the surface of NL by 'click chemistry' proceeded easily and almost quantitatively at 25°C in our experimental conditions. Among different nanoparticles suitable for click chemistry [44], or already utilized for coupling with Curc [30,41], we decided to use nanoliposomes, due to their known non-toxic and non-immunogenic features, fully biodegradable and structurally versatile nature [45].…”

Section: Discussionmentioning

confidence: 99%

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Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

Sancini

Gregori

Salvati

et al. 2013

J Nanomedic Nanotechnol

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# These authors contributed equally to this work preventing high-molecular weight molecules from passing through [25]. Indeed, the design and engineering of NP with high specificity for brain capillary endothelial cells have been proposed as promising strategy for AD diagnosis and treatment [26][27][28][29].The aim of the present investigation was to design NP able to bind Aβ peptide and to cross the BBB. To reach this goal we developed nanoliposomes (NL) double-functionalized with a curcuminderivative and with a modified HIV Transactivating Transcriptional Activator (TAT) peptide. Preparation of NL covalently decorated with curcumin-derivative was previously carried out, starting from a curcumin alkyne-derivative showing a very high affinity for Aβ peptide [30], suitable for NL decoration by click chemistry and with improved features of stability with respect to curcumin itself [31]. On the other side, TAT-peptide could enhance NP BBB crossing [32,33] based on the evidence that its coupling to NP may facilitate their efficient translocation through the cell membrane, bypassing the endocytic pathway [34][35][36]. TAT-peptide was covalently attached to NL surface via a thiol-maleimide reaction. The ability of NL to bind Aβ after AbstractProduction of abnormally high amounts of amyloid-β peptide in the brain plays a central role in the onset and development of Alzheimer's disease, a neurodegenerative disorder affecting millions of individuals worldwide. Nanoparticles have been proposed as promising tools to treat the disease by delivering drugs and contrast agents to the brain. Here, nanoliposomes decorated with a curcumin-derivative, displaying high affinity for amyloid-β, were functionalized with a modified cell-penetrating TAT-peptide, with the aim of conferring on such nanoliposomes the ability to cross the blood-brain barrier. Functionalization with TAT-peptide did not modify the ability of curcumindecorated nanoliposomes to bind amyloid-β fibrils, as assessed by surface plasmon resonance. Confocal microscopy, mass spectrometry and radioactivity experiments with [3 H]-sphingomyelin showed about 3-fold increase in the uptake of nanoliposomes by human brain capillary endothelial cells (hCMEC/D3) after the functionalization with TATpeptide, with no alterations in cell viability. Moreover, TAT functionalization increased the permeability of curcuminnanoliposomes across a blood-brain barrier model made with the same cells. The similar permeabilities of curcuminderivative and [3 H]-sphingomyelin suggested that nanoliposomes were transported intact. Considering these results, nanoliposomes functionalized with the curcumin-derivative and TAT-peptide represent a promising tool for targeting amyloid-β directly in the brain parenchyma.

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Section: Discussionmentioning

confidence: 99%

“…Aβ aggregates were prepared as already described [38] and immobilized on a COOH5 sensor chip (ICx Technologies) by amine coupling chemistry using the same procedure described by Le Droumaguet et al [41]. The final immobilization level was ~5000 Response Unit (RU, 1 RU = 1 pg/mm²).…”

Section: Interaction Of Nl With Aβ Investigated By Surface Plasmon Rementioning

confidence: 99%

Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

Sancini

Gregori

Salvati

et al. 2013

J Nanomedic Nanotechnol

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“…Particles, spontaneously formed in the mixer chamber, were evacuated by the outlet jet, and then quenched in 25 mL of water under magnetic stirring. Finally, the acetone was evaporated in Valente et al -eXPRESS Polymer Letters Vol.7, No.1 (2013) [2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] a rotating device (30 minutes at room temperature) to obtain an aqueous suspension of nanospheres. Nanocapsules were prepared by the same procedure after adding 200 #L of Miglyol 812 (i.e.…”

Section: Preparation Of Unloaded and Triclosanmentioning

confidence: 99%

“…It was also demonstrated that nanoparticles have an adequate density of MePEG chains on their surface to provide enhanced stability in the blood compartment and ensure a long circulating characteristic [13,14]. Nanoparticles of poly(alkyl cyanoacrylate) amphiphilic copolymers have recently been successfully used for other biomedical applications such as human brain endothelial cell imaging [15] and early Alzheimer's disease diagnosis and treatment [16]. Drug loaded nanoparticles of poly(MePEGCA-co-HDCA) have also recently been prepared using a new methodology based on solvent displacement in confined impinging jet mixers (CIJM) [17].…”

mentioning

confidence: 99%

Nanospheres and nanocapsules of amphiphilic copolymers constituted by methoxypolyethylene glycol cyanoacrylate and hexadecyl cyanoacrylate units

Valente¹,

Valle²,

Casas³

et al. 2013

Express Polym. Lett.

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Nanospheres and nanocapsules of an amphiphilic copolymer having methylated polyethylene glycol and hexadecyl lateral groups were prepared by the solvent displacement method and using confined impinging jet mixers. Degradation, thermal properties and crystalline structure were investigated. Interestingly, pegylated chains hydrolyzed through ester bond cleavage, whereas the more hydrophobic hexadecyl ester groups were resistant to degradation in aqueous media. The copolymer crystallized from the melt, giving rise to spherulites with a negative birefringence and domains corresponding to crystallization of the different lateral groups. Size distribution and morphology of nanoparticles were mainly evaluated by electron microscopy. Nanocapsules were characterized by a stable membrane with a thickness close to 5 nm that allowed efficient encapsulation of a triglyceride oil. Triclosan was selected as an example of a hydrophobic drug to be loaded in both nanospheres and nanocapsules. The release behavior of these dosage forms was clearly different. Thus, the Burst effect was practically suppressed when using nanocapsules; in addition, these showed a sustained, controlled release over a greater time period. Antimicrobial activity of triclosan loaded nanospheres and nanocapsules was evaluated using Gram-negative and Gram-positive bacteria. The former were highly sensitive to the released triclosan whereas the latter strongly depended on the number of particles in the culture medium

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“…GALA's transition from random coil to an amphiphilic α-helix roughly occurs when the pH is decreased from 7 to 5, the pH of inflection between the two conformational states was reported to be near pH 6. [9][10][11][12] At low pHs the Glu sites are protonated and uncharged. The hydrophobic periodicity of the EALA repeats allows the peptide to fold into a stable amphiphilic helix with hydrophobic leucine and alanine sites on one, and hydrophilic glutamic acids on the other side of the helix (Scheme 1).…”

Section: Introductionmentioning

confidence: 99%

Sticky water surfaces: Helix–coil transitions suppressed in a cell-penetrating peptide at the air-water interface

Schach

Globisch

Roeters

et al. 2014

The Journal of Chemical Physics

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Sticky water surfaces: Helix-coil transitions suppressed in a cell-penetrating peptide at the air-water interface Schach, D.; Globisch, C.; Roeters, S.J.; Woutersen, S.; Fuchs, A.; Weiss, C.K.; Backus, E.H.G.; Landfester, K.; Bonn, M.; Peter, C.; Weidner, T. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. GALA is a 30 amino acid synthetic peptide consisting of a Glu-Ala-Leu-Ala repeat and is known to undergo a reversible structural transition from a disordered to an α-helical structure when changing the pH from basic to acidic values. In its helical state GALA can insert into and disintegrate lipid membranes. This effect has generated much interest in GALA as a candidate for pH triggered, targeted drug delivery. GALA also serves as a well-defined model system to understand cell penetration mechanisms and protein folding triggered by external stimuli. Structural transitions of GALA in solution have been studied extensively. However, cell penetration is an interfacial effect and potential biomedical applications of GALA would involve a variety of surfaces, e.g., nanoparticles, lipid membranes, tubing, and liquid-gas interfaces. Despite the apparent importance of interfaces in the functioning of GALA, the effect of surfaces on the reversible folding of GALA has not yet been studied. Here, we use sum frequency generation vibrational spectroscopy (SFG) to probe the structural response of GALA at the air-water interface and IR spectroscopy to follow GALA folding in bulk solution. We combine the SFG data with molecular dynamics simulations to obtain a molecularlevel picture of the interaction of GALA with the air-water interface. Surprisingly, while the fully reversible structural transition was observed in solution, at the water-air interface, a large fraction of the GALA population remained helical at high pH. This "stickiness" of the air-water interface can be explained by the stabilizing interactions of hydrophobic leucine and alanine side chains with the water surface. © 2014 AIP Publishing LLC. [http://dx

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Versatile and Efficient Targeting Using a Single Nanoparticulate Platform: Application to Cancer and Alzheimer’s Disease

Cited by 130 publications

References 54 publications

Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

Functionalization with TAT-Peptide Enhances Blood-Brain Barrier Crossing In vitro of Nanoliposomes Carrying a Curcumin-Derivative to Bind Amyloid-Β Peptide

Nanospheres and nanocapsules of amphiphilic copolymers constituted by methoxypolyethylene glycol cyanoacrylate and hexadecyl cyanoacrylate units

Sticky water surfaces: Helix–coil transitions suppressed in a cell-penetrating peptide at the air-water interface

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