Abstract 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.
Wang et al. (Thu,) studied this question.
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