We
developed dendritic caged molecular glues (CagedGlue-R)
as tags for nucleus-targeted drug delivery, whose multiple guanidinium
ion (Gu+) pendants are protected by an anionic photocleavable
unit (butyrate-substituted nitroveratryloxycarbonyl; BANVOC). Negatively charged CagedGlue-R hardly binds to
anionic biomolecules because of their electrostatic repulsion. However,
upon exposure of CagedGlue-R to UV light or near-infrared
(NIR) light, the BANVOC groups of CagedGlue-R
are rapidly detached to yield an uncaged molecular glue (UncagedGlue-R) that carries multiple Gu+ pendants. Because Gu+ forms a salt bridge with PO4–, UncagedGlue-R tightly adheres to anionic biomolecules
such as DNA and phospholipids in cell membranes by a multivalent salt-bridge
formation. When tagged with CagedGlue-R, guests can be
taken up into living cells via endocytosis and hide in endosomes.
However, when the CagedGlue-R tag is photochemically uncaged
to form UncagedGlue-R, the guests escape from the endosome
and migrate into the cytoplasm followed by the cell nucleus. We demonstrated
that quantum dots (QDs) tagged with CagedGlue-R can be
delivered efficiently to cell nuclei eventually by irradiation with
light.