Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide

Re, Francesca; Cambianica, Ilaria; Sesana, Silvia; Salvati, Elisa; Cagnotto, Alfredo; Salmona, Mario; Couraud, Pierre Olivier; Moghimi, S. Moein; Masserini, Massimo; Sancini, Giulio

doi:10.1016/j.jbiotec.2011.06.037

Cited by 96 publications

(93 citation statements)

References 18 publications

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“…After purification of TAT-Curc-NL from the unbound peptide by gel filtration, fluorescence emission spectrum was recorded to verify the presence of TAT-peptide onto NL. The tryptophan fluorescence spectrum of TAT-Curc-NL displayed a blue shift to 350 nm in the emission maximum, with respect to 354 nm of TAT-peptide alone ( Figure 3B), suggesting that the coupling of TAT with the mal-PEG-DSPE lipid occurred, as previously reported for other peptides [42]. The yield of coupling was between 60 and 70%.…”

Section: Curc-nl and Tat-curc-nl Preparation And Characterizationsupporting

confidence: 79%

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: Curc-nl and Tat-curc-nl Preparation And Characterizationsupporting

confidence: 79%

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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“…16,17 SKNSH human neuroblastoma cells (commercially purchased from American Type Culture Collection, Manassas, VA, USA) were maintained in Dulbecco's Modified Eagle's Medium supplemented with 10% heat-inactivated fetal bovine serum, penicillin (100 U/mL), streptomycin (100 µg/mL), and l-glutamine (2 mM) in a 5% CO 2 humidified incubator at 37°C. The cells were differentiated with 10 µM retinoic acid for 5 days.…”

Section: Cell Culturesmentioning

confidence: 99%

“…17 After this, cells were detached from the plate with trypsin for 15 minutes. Cell pellets were suspended in 1 mL phosphate-buffered saline and digested by adding 4 mL of aqua regia (HNO 3 65% and HCl 37%; Sigma-Aldrich).…”

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confidence: 99%

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Orlando¹,

Cazzaniga²,

Tringali³

et al. 2017

IJN

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Purpose Mesoporous silica nanoparticles (MSNPs) are excellent candidates for biomedical applications and drug delivery to different human body areas, the brain included. Although toxicity at cellular level has been investigated, we are still far from using MSNPs in the clinic, because the mechanisms involved in the cellular responses activated by MSNPs have not yet been elucidated. Materials and methods This study used an in vitro multiparametric approach to clarify relationships among size, dose, and time of exposure of MSNPs (0.05–1 mg/mL dose range), and cellular responses by analyzing the morphology, viability, and functionality of human vascular endothelial cells and neurons. Results The results showed that 24 hours of exposure of endothelial cells to 250 nm MSNPs exerted higher toxicity in terms of mitochondrial activity and membrane integrity than 30 nm MSN at the same dose. This was due to induced cell autophagy (in particular mitophagy), probably consequent to MSNP cellular uptake (>20%). Interestingly, after 24 hours of treatment with 30 nm MSNPs, very low MSNP uptake (<1%) and an increase in nitric oxide production (30%, P <0.01) were measured. This suggests that MSNPs were able to affect endothelial functionality from outside the cells. These differences could be attributed to the different protein-corona composition of the MSNPs used, as suggested by sodium dodecyl sulfate polyacrylamide-gel electrophoresis analysis of the plasma proteins covering the MSNP surface. Moreover, doses of MSNPs up to 0.25 mg/mL perturbed network activity by increasing excitability, as detected by multielectrode-array technology, without affecting neuronal cell viability. Conclusion These results suggest that MSNPs may be low-risk if prepared with a diameter <30 nm and if they reach human tissues at doses <0.25 mg/mL. These important advances could help the rational design of NPs intended for biomedical uses, demonstrating that careful toxicity evaluation is necessary before using MSNPs in patients.

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“…A catalogue of potential BBB-crossing peptides and proteins for functionalization is available (Van et al, 2012) (Spencer and Verma, 2007b); ApoE (Re et al, 2011;Wagner et al, 2012) and Apo A-I (Fioravanti et al, 2012;Kratzer et al, 2007), have been already used to functionalize diverse types of drugs and nanoparticles to allow or enhance BBB crossing. Others, such as Kunitzderived peptides (Angiopeps), presented in plain protein-drug complexes, have entered…”

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confidence: 99%

Targeting low-density lipoprotein receptors with protein-only nanoparticles

Céspedes

Unzueta

et al. 2015

J Nanopart Res

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35Low density lipoprotein receptors (LDLR) are appealing cell surface targets in drug delivery, as they are expressed in the blood-brain barrier (BBB) endothelium and are able to mediate transcytosis of functionalized drugs for molecular therapies of the central nervous system (CNS). On the other hand, brain-targeted drug delivery is currently limited, among others, by the poor availability of biocompatible vehicles, as 40 most of the nanoparticles under development as drug carriers pose severe toxicity issues. In this context, protein nanoparticles offer functional versatility, easy and costeffective bioproduction and full biocompatibility. In this study, we have designed and

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Functionalization with ApoE-derived peptides enhances the interaction with brain capillary endothelial cells of nanoliposomes binding amyloid-beta peptide

Cited by 96 publications

References 18 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

Mesoporous silica nanoparticles trigger mitophagy in endothelial cells and perturb neuronal network activity in a size- and time-dependent manner

Targeting low-density lipoprotein receptors with protein-only nanoparticles

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