Browsing by Author "Enciso, Eduardo"
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Item Lipid nanoparticles for antisense oligonucleotide gene interference into brain border-associated macrophages.(Frontiers in Molecular Biosciences, 2022) Calero, Macarena; Moleiro, Lara H.; Sayd, Aline; Dorca, Yeray; Miquel-Rio, Lluis; Paz, Verónica; Robledo-Montaña, Javier; Enciso, Eduardo; Acción, Fernando; Herráez Aguilar, Diego; Hellweg, Thomas; Sánchez, Luis; Bortolozzi, Analía; Leza, Juan C.; García-Bueno, Borja; Monroy, FranciscoA colloidal synthesis’ proof-of-concept based on the Bligh–Dyer emulsion inversion method was designed for integrating into lipid nanoparticles (LNPs) cell-permeating DNA antisense oligonucleotides (ASOs), also known as GapmeRs (GRs), for mRNA interference. The GR@LNPs were formulated to target brain border-associated macrophages (BAMs) as a central nervous system (CNS) therapy platform for silencing neuroinflammation-related genes. We specifically aim at inhibiting the expression of the gene encoding for lipocalin-type prostaglandin D synthase (L-PGDS), an anti-inflammatory enzyme expressed in BAMs, whose level of expression is altered in neuropsychopathologies such as depression and schizophrenia. The GR@LNPs are expected to demonstrate a bio-orthogonal genetic activity reacting with L-PGDS gene transcripts inside the living system without interfering with other genetic or biochemical circuitries. To facilitate selective BAM phagocytosis and avoid subsidiary absorption by other cells, they were functionalized with a mannosylated lipid as a specific MAN ligand for the mannose receptor presented by the macrophage surface. The GR@LNPs showed a high GR-packing density in a compact multilamellar configuration as structurally characterized by light scattering, zeta potential, and transmission electronic microscopy. As a preliminary biological evaluation of the mannosylated GR@LNP nanovectors into specifically targeted BAMs, we detected in vivo gene interference after brain delivery by intracerebroventricular injection (ICV) in Wistar rats subjected to gene therapy protocol. The results pave the way towards novel gene therapy platforms for advanced treatment of neuroinflammation-related pathologies with ASO@LNP nanovectors.Item Moulding hydrodynamic 2D-crystals upon parametric Faraday waves in shear-functionalized water surfaces.(Nature Communications, 2021) Kharbedia, Mikheil; Caselli, Niccolò; Herráez Aguilar, Diego; López Menéndez, Horacio; Enciso, Eduardo; Santiago, José A.; Monroy, FranciscoFaraday waves, or surface waves oscillating at half of the natural frequency when a liquid is vertically vibrated, are archetypes of ordering transitions on liquid surfaces. Although unbounded Faraday waves patterns sustained upon bulk frictional stresses have been reported in highly viscous fluids, the role of surface rigidity has not been investigated so far. Here, we demonstrate that dynamically frozen Faraday waves—that we call 2D-hydrodynamic crystals—do appear as ordered patterns of nonlinear gravity-capillary modes in water surfaces functionalized with soluble (bio)surfactants endowing in-plane shear stiffness. The phase coherence in conjunction with the increased surface rigidity bears the Faraday waves ordering transition, upon which the hydrodynamic crystals were reversibly molded under parametric control of their degree of order, unit cell size and symmetry. The hydrodynamic crystals here discovered could be exploited in touchless strategies of soft matter and biological scaffolding ameliorated under external control of Faraday waves coherence.