Azobenzene-bridged ionizable amphiphilic Janus glycosides for lightcontrolled, single-component and organmodulable pDNA delivery

Stimuli-responsive supramolecular systems enable spatiotemporal control of nucleic acid (NA) delivery. To achieve precise and programmable vectors, we designed azobenzene-bridged ionizable amphiphilic Janus glycosides (IAJGs) as single-component, light-responsive DNA carriers. These glucopyranose-ba...

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Detalles Bibliográficos
Autores: Wang, Zhaoxin, Rivero Barbarroja, Gonzalo, Benito, Juan M., Maisonneuve, Stéphane, Vélaz, Itziar, Juárez Gonzálvez, Inmaculada, Garrido, María J., Tros de Ilarduya, Conchita, Ortiz Mellet, Carmen, Xie, Juan, García Fernández, José M.
Tipo de recurso: artículo
Estado:Versión publicada
Fecha de publicación:2026
País:España
Institución:Universidad de Sevilla (US)
Repositorio:idUS. Depósito de Investigación de la Universidad de Sevilla
OAI Identifier:oai:dnet:idus________::e78772c89f96fbb069f6e79146dedcbf
Acceso en línea:https://hdl.handle.net/11441/186622
https://doi.org/10.1038/s42004-026-01920-z
Access Level:acceso abierto
Descripción
Sumario:Stimuli-responsive supramolecular systems enable spatiotemporal control of nucleic acid (NA) delivery. To achieve precise and programmable vectors, we designed azobenzene-bridged ionizable amphiphilic Janus glycosides (IAJGs) as single-component, light-responsive DNA carriers. These glucopyranose-based dimers undergo reversible E/Z photoisomerization while forming stable nanocomplexes with plasmid DNA (pDNA). Photoisomerization alters nanocomplex size, surface charge, and internal order, resulting in distinct transfection outcomes. In vitro, O- and S-glycoside derivatives displayed isomer-dependent activity across COS-7, HepG2, and RAW264.7 cells, with pronounced switching effects specially in macrophages. In vivo, systemic administration revealed organ-selective responses:O-glycosides shifted expression from liver to lung upon E→Z conversion, whereas S-glycosides favored spleen targeting. All formulations maintained high cell viability. These results highlight photoswitchable IAJGs as structurally defined vectors for adjustable control over NA delivery and organ tropism.