Artículo
Mannosyl-coated nanocomplexes from amphiphilic cyclodextrins and pDNA for site-specific gene delivery
Autor/es | Díaz Moscoso, Alejandro
Guilloteau, Nicolas Bienvenu, Céline Méndez Ardoy, Alejandro Jiménez Blanco, José Luis Benito Hernández, Juan Manuel Le Gourriérec, Loïc Di Giorgio, Christophe Vierling, Pierre Defaye, Jacques Ortiz Mellet, Carmen García Fernández, José Manuel |
Departamento | Universidad de Sevilla. Departamento de Química orgánica |
Fecha de publicación | 2011-10 |
Fecha de depósito | 2024-04-11 |
Publicado en |
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Resumen | Fully homogeneous facial amphiphiles consisting in a cyclodextrin (CD) platform onto which a polycationic cluster and a multi-tail hydrophobic moiety have been installed (polycationic amphiphilic CDs; paCDs) self-organized ... Fully homogeneous facial amphiphiles consisting in a cyclodextrin (CD) platform onto which a polycationic cluster and a multi-tail hydrophobic moiety have been installed (polycationic amphiphilic CDs; paCDs) self-organized in the presence of plasmid DNA to form nanometric complexes (CDplexes) which exhibit broad-range transfection capabilities. We hypothesized that biorecognizable moieties located at the hydrophilic rim in the CD scaffold would be exposed at the surface of the corresponding nanoparticles after DNA-promoted aggregation, endowing the system with molecular recognition abilities towards cell receptors. This concept has been demonstrated by developing an efficient synthetic strategy for the preparation of multivalent polycationic glyco-amphiphilic CDs (pGaCDs). Self-assembled nanoparticles obtained from mannosylated pGaCDs and pDNA (average hydrodynamic diameter 80 nm) have been shown to be specifically recognized by mannose-specific lectins, including concanavalin A (Con A) and the human macrophage mannose receptor (MMR). Further macrophage adhesion studies indicated that unspecific binding, probably due to electrostatic interactions with negatively charged cell membrane components, can also operate. The relative specific versus non-specific internalization is dependent on the pGaCD:pDNA proportion, being optimal at a protonable nitrogen/phosphate (N/P) ratio of 5. The resulting GlycoCDplexes were shown to specifically mediate transfection in Raw 264.7 (murine macrophage) cells expressing the mannose-fucose receptor in vitro. FACS experiments confirmed that transfection using these nanoparticles is mannose-dependent, supporting the potential of the approach towards vectorized gene delivery. |
Agencias financiadoras | Ministerio de Ciencia e Innovación (MICIN). España Junta de Andalucía |
Identificador del proyecto | SAF2010-15670
CTQ2010-15848 P06-FQM-01601 |
Cita | Díaz Moscoso, A., Guilloteau, N., Bienvenu, C., Méndez Ardoy, A., Jiménez Blanco, J.L., Benito Hernández, J.M.,...,García Fernández, J.M. (2011). Mannosyl-coated nanocomplexes from amphiphilic cyclodextrins and pDNA for site-specific gene delivery. Biomaterials, 32 (29), 7263-7273. https://doi.org/10.1016/j.biomaterials.2011.06.025. |
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Mannosyl-coated nanocomplexes_C.pdf | 1.527Mb | [PDF] | Ver/ | Versión aceptada |