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<p>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 <i>E/Z</i> 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, <i>O</i>- and <i>S</i>-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: <i>O</i>-glycosides shifted expression from liver to lung upon <i>E</i> → <i>Z</i> conversion, whereas <i>S</i>-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.</p><p></p>

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Azobenzene-bridged ionizable amphiphilic Janus glycosides for light-controlled, single-component and organ-modulable pDNA delivery

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月5日

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  • Zhaoxin Wang,
  • Gonzalo Rivero-Barbarroja,
  • Juan M. Benito,
  • Stéphane Maisonneuve,
  • Itziar Vélaz,
  • Inmaculada Juárez-Gonzálvez,
  • María J. Garrido,
  • Conchita Tros de Ilarduya,
  • Carmen Ortiz Mellet,
  • Juan Xie,
  • José M. García Fernández

摘要

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.