Sulfobetaine-Phosphonate Block Copolymer Coated Iron Oxide Nanoparticles for Genomic Locus Targeting and Magnetic Micromanipulation in the Nucleus of Living Cells

Exerting forces on biomolecules inside living cells wouldallowus to probe their dynamic interactions in their native environment.Magnetic iron oxide nanoparticles represent a unique tool capableof pulling on biomolecules with the application of an external magneticfield gradient; however, their use has been restricted to biomoleculesaccessible from the extracellular medium. Targeting intracellularbiomolecules represents an additional challenge due to potential nonspecificinteractions with cytoplasmic or nuclear components. We present thesynthesis of sulfobetaine-phosphonate block copolymer ligands, whichprovide magnetic nanoparticles that are stealthy and targetable inliving cells. We demonstrate, for the first time, their efficienttargeting in the nucleus and their use for magnetic micromanipulationof a specific genomic locus in living cells. We believe that thesestable and sensitive magnetic nanoprobes represent a promising toolto manipulate specific biomolecules in living cells and probe themechanical properties of living matter at the molecular scale.