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

Department of Chemistry and Biotechnology,
School of Engineering,
Department of Chemistry and Biotechnology, School of Engineering

University of Tokyo

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

Akio Arisaka

.css-o250i3{font-size:18px;font-family:Open Sans,sans-serif;line-height:21.6px;}Department of Chemistry and Biotechnology,School of Engineering,Department of Chemistry and Biotechnology, School of Engineering

University of Tokyo

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

Department of Chemistry and Biotechnology,
School of Engineering,
Department of Chemistry and Biotechnology, School of Engineering