title: The PEG-fluorochrome shielding approach for targeted probe design.
abstract: We provide a new approach for fluorescent probe design termed "PEG-fluorochrome shielding", where PEGylation enhances quantum yields while blocking troublesome interactions between fluorochromes and biomolecules. To demonstrate PEG-fluorochrome shielding, fluorochrome-bearing peptide probes were synthesized, three without PEG and three with a 5 kDa PEG functional group. In vitro, PEG blocked the interactions of fluorochrome-labeled peptide probes with each other (absorption spectra, self-quenching) and reduced nonspecific interactions with cells (by FACS). In vivo, PEG blocked interactions with biomolecules that lead to probe retention (by surface fluorescence). Integrin targeting in vivo was obtained as the differential uptake of an (111)In-labeled, fluorochrome-shielded, integrin-binding RGD probe and a control RAD. Using PEG to block fluorochrome-mediated interactions, rather than synthesizing de novo fluorochromes, can yield new approaches for the design of actively or passively targeted near-infrared fluorescent probes.
authors.affiliation: Center for Translational Nuclear Medicine and Molecular Imaging, Massachusetts General Hospital, 149 13th Street, Charlestown, Massachusetts 02129, USA.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Guo
authors.forename: Hushan
authors.initials: H
authors.lastname: Yuan
authors.forename: William L
authors.initials: WL
authors.lastname: Rice
authors.forename: Anand T N
authors.initials: AT
authors.lastname: Kumar
authors.forename: Craig J
authors.initials: CJ
authors.lastname: Goergen
authors.forename: Kimmo
authors.initials: K
authors.lastname: Jokivarsi
authors.forename: Lee
authors.initials: L
authors.lastname: Josephson
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005456:Fluorescent Dyes / Q000008:administration & dosage / Q000737:chemistry; D006801:Humans; D051379:Mice; D015335:Molecular Probes / Q000008:administration & dosage / Q000138:chemical synthesis; D015394:Molecular Structure; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D015335:Molecular Probes; D010455:Peptides; D011092:Polyethylene Glycols