title: Designing Molecular Probes To Prolong Intracellular Retention: Application to Nitroxide Spin Probes.
abstract: Targeted delivery of molecular probes into cells enables cellular imaging through optical and magnetic modalities. Probe molecules that are well retained by cells can accumulate to higher intracellular concentrations, and thus increase the signal-to-noise ratio of, and widen the temporal window for, imaging. Here we synthesize a paramagnetic spin probe bearing six ionic functional groups and show that it has long intracellular half-life (>12 h) and exceptional biostability in living cells. We demonstrate that judicious incorporation of ionic substituents on probe molecules systematically increases intracellular retention time, and should therefore be beneficial to imaging experiments.
authors.affiliation: Center for Biomedical Engineering & Technology, and Department of Physiology, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Legenzov
authors.affiliation: Center for Biomedical Engineering & Technology, and Department of Physiology, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States.
authors.forename: Sukumaran
authors.initials: S
authors.lastname: Muralidharan
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208, United States.
authors.forename: Lukas B
authors.initials: LB
authors.lastname: Woodcock
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208, United States.
authors.forename: Gareth R
authors.initials: GR
authors.lastname: Eaton
authors.affiliation: Department of Chemistry and Biochemistry, University of Denver , Denver, Colorado 80208, United States.
authors.forename: Sandra S
authors.initials: SS
authors.lastname: Eaton
authors.affiliation: Department of Pharmaceutical Sciences, School of Pharmacy, and Center for Biomedical Engineering & Technology, School of Medicine, University of Maryland , Baltimore, Maryland 21201, United States.
authors.forename: Gerald M
authors.initials: GM
authors.lastname: Rosen
authors.affiliation: Center for Biomedical Engineering & Technology, and Department of Physiology, University of Maryland School of Medicine , Baltimore, Maryland 21201, United States.
authors.forename: Joseph P Y
authors.identifier: http://orcid.org/0000-0002-8875-2180
authors.initials: JP
authors.lastname: Kao
mesh_terms: D060326:Chemistry Techniques, Synthetic; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D006207:Half-Life; D006801:Humans; D019169:Jurkat Cells; D015335:Molecular Probes / Q000737:chemistry* / Q000493:pharmacokinetics*; D009589:Nitrogen Oxides / Q000737:chemistry; D013113:Spin Labels
chemical_list: D015335:Molecular Probes; D009589:Nitrogen Oxides; D013113:Spin Labels; C039900:nitroxyl