Descripción del proyecto
Nanosondas a base de glicanos para administrar antibióticos en las bacterias
Los carbohidratos de la superficie celular desempeñan papeles esenciales en la adhesión bacteriana. Estas interacciones presentan un nivel elevado de especificidad y una afinidad débil hacia sus ligandos de carbohidrato, lo cual se compensa por la presentación por parte del hospedador de ligandos de carbohidrato de forma multivalente o en forma de agrupaciones en la superficie mucosa o celular. Un disacárido puede actuar como transportador en nanopartículas fluorescentes bifuncionalizadas para contribuir a la administración intracelular de otras porciones de glicanos no internalizables, evitando así la vía de degradación lisosómica o endosómica. Unos nanomateriales a base de carbono fluorescentes, no tóxicos y solubles en agua desarrollados recientemente han mostrado capacidades para marcar bacterias tanto grampositivas como gramnegativas. El proyecto BioNanoProbes, financiado con fondos europeos, tiene como objetivo desarrollar una nueva clase de nanosondas a base de glicanos para marcar y administrar antibióticos en las bacterias.
Objetivo
Methods for specific recognition and targeting of bacteria are of key importance in developing approaches to counter the growth of antimicrobial resistance (AMR). Cell surface carbohydrates play key roles in cell recognition mechanisms and bacterial adhesion. These key interactions typically exhibit high specificity and weak affinities toward their carbohydrate ligand. This low affinity is compensated in nature by the architecture of the protein, the host presenting the carbohydrate ligands in a multivalent manner or as clusters on the cell or mucosal surface. Glyco-nanomaterials offer the possibility of attaching several different molecules to the same nanoparticle while controlling the relative densities of these ligands. Recently, the Galan group demonstrated that a simple disaccharide, such as lactose can act as a “Trojan horse” on bi-functionalized fluorescent nanopartiples (CdSe QDs) to help intracellular delivery of other non-internalizable glycan moieties and largely avoid the endosomal/lysosomal degradative pathway. Following this, the group has developed a new class of water-soluble, non-toxic fluorescent carbon-based nanomaterials which are easily accessible from cheap carbohydrate starting materials and more excitingly, preliminary data have shown that these new carbon nanodots are able to label both Gram-negative and Gram-positive bacteria. Based on these exciting results, the aim of this project is to develop a new class of glycan-based nanoprobes for labelling and delivery of antibiotics into bacteria. The glycan-based nano pro-drugs will be evaluated in bacterial binding and killing assays and screened for selective labelling and drug release using confocal microscopy and TEM. This is a multidisciplinary project involving synthetic organic and materials chemistry, glycobiology and microbiology.
Ámbito científico
- natural sciencesbiological sciencesmicrobiologybacteriology
- natural sciencesbiological sciencesbiochemistrybiomoleculesproteins
- natural sciencesbiological sciencesbiochemistrybiomoleculescarbohydrates
- natural sciencesphysical sciencesopticsmicroscopyconfocal microscopy
- medical and health sciencesbasic medicinepharmacology and pharmacydrug resistanceantibiotic resistance
Palabras clave
Programa(s)
Régimen de financiación
MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF)Coordinador
BS8 1QU Bristol
Reino Unido