Journal de la nanomédecine et de la nanotechnologie

Abstrait

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

Giulio Sancini, Maria Gregori, Elisa Salvati, Ilaria Cambianica, Francesca Re, Francesca Ornaghi, Mara Canovi, Claudia Fracasso, Alfredo Cagnotto, Miriam Colombo, Cristiano Zona, Marco Gobbi, Mario Salmona, Barbara La Ferla, Francesco Nicotra and Massimo Masserini

Production 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 [3H]-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 [3H]-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.