spatiotemporally-controlled-nuclear-translocation-guests-living-cells

Spatiotemporally Controlled Nuclear Translocation of Guests in Living Cells Using Caged Molecular Glues as Photoactivatable Tags

The cell nucleus is one of the most important organelles as a subcellular drug-delivery target, since modulation of gene replication and expression is ...

University of Tokyo

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

Akio Arisaka

Biography

JoVE Journal Publications

Other Publications