Person:
Cañadas Benito, Olga

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First Name
Olga
Last Name
Cañadas Benito
URI
https://hdl.handle.net/20.500.14352/74363
Affiliation
Universidad Complutense de Madrid
Faculty / Institute
Ciencias Biológicas
Department
Bioquímica y Biología Molecular
Area
Bioquímica y Biología Molecular
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2016 - 20182
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Author: Casals Carro, María Cristina × Author: Cañadas Benito, Olga × Start date: 2016 × Subject: 577.112 ×

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Now showing 1 - 2 of 2
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    Conserved bacterial-binding peptides of the scavenger-like human lymphocyte receptor CD6 protect from mouse experimental sepsis
    (Frontiers in Immunology, 2018) Martínez Florensa, Mario; Català, Cristina; Velasco de Andrés, María; Cañadas Benito, Olga; Fraile Ágreda, Víctor; Casadó Llombart, Sergi; Armiger Borràs, Noelia; Consuegra Fernández, Marta; Casals Carro, María Cristina; Lozano, Francisco; Kishore, Uday
    Sepsis is an unmet clinical need constituting one of the most important causes of death worldwide, a fact aggravated by the appearance of multidrug resistant strains due to indiscriminate use of antibiotics. Host innate immune receptors involved in pathogen-associated molecular patterns (PAMPs) recognition represent a source of broad-spectrum therapies alternative or adjunctive to antibiotics. Among the few members of the ancient and highly conserved scavenger receptor cysteine-rich superfamily (SRCR-SF) sharing bacterial-binding properties there is CD6, a lymphocyte-specific surface receptor. Here, we analyze the bacterial-binding properties of three conserved short peptides (11-mer) mapping at extracellular SRCR domains of human CD6 (CD6.PD1, GTVEVRLEASW; CD6.PD2 GRVEMLEHGEW; and CD6.PD3, GQVEVHFRGVW). All peptides show high binding affinity for PAMPs from Gram-negative (lipopolysaccharide; Kd from 3.5 to 3,000 nM) and Gram-positive (lipoteichoic acid; Kd from 36 to 680 nM) bacteria. The CD6.PD3 peptide possesses broad bacterial-agglutination properties and improved survival of mice undergoing polymicrobial sepsis in a dose- and time-dependent manner. Accordingly, CD6.PD3 triggers a decrease in serum levels of both pro-inflammatory cytokines and bacterial load. Interestingly, CD6.PD3 shows additive survival effects on septic mice when combined with Imipenem/Cilastatin. These results illustrate the therapeutic potential of peptides retaining the bacterial-binding properties of native CD6.
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    Pulmonary surfactant protein A-mediated enrichment of surface-decorated polymeric nanoparticles in alveolar macrophages
    (Molecular Pharmaceutics, 2016) Ruge, Christian A.; Hillaireau, Hervé; Grabowski, Nadège; Beck-Broichsitter, Mortiz; Cañadas Benito, Olga; Tsapis, Nicolas; Casals Carro, María Cristina; Nicolas, Julien; Fattal, Elias
    Surfactant protein A (SP-A), a lung anti-infective protein, is a lectin with affinity for sugars found on fungal and micrococcal surfaces such as mannose. We synthesized a mannosylated poly(lactic acid)-poly(ethylene glycol) (PLA-PEG) copolymer and used it to produce nanoparticles with a polyester (PLGA/PLA) core and a PEG shell decorated with mannose residues, designed to be strongly associated with SP-A for an increased uptake by alveolar macrophages. Nanoparticles made of the copolymers were obtained by nanoprecipitation and displayed a size of around 140 nm. The presence of mannose on the surface was demonstrated by zeta potential changes according to pH and by a strong aggregation in the presence of concanavalin A. Mannosylated nanoparticles bound to SP-A as demonstrated by dynamic light scattering and transmission electron microscopy. The association with SP-A increased nanoparticle uptake by THP-1 macrophages in vitro. In vivo experiments demonstrated that after intratracheal administration of nanoparticles with or without SP-A, SP-A-coated mannosylated nanoparticles were internalized by alveolar macrophages in greater proportion than SP-A-coated nonmannosylated nanoparticles. The data demonstrate for the first time that the pool of nanoparticles available to lung cells can be changed after surface modification, using a biomimetic approach.