title: pHLIP-FIRE, a cell insertion-triggered fluorescent probe for imaging tumors demonstrates targeted cargo delivery in vivo.
abstract: We have developed an improved tool for imaging acidic tumors by reporting the insertion of a transmembrane helix: the pHLIP-Fluorescence Insertion REporter (pHLIP-FIRE). In acidic tissues, such as tumors, peptides in the pHLIP family insert as α-helices across cell membranes. The cell-inserting end of the pHLIP-FIRE peptide has a fluorophore-fluorophore or fluorophore-quencher pair. A pair member is released by disulfide cleavage after insertion into the reducing environment inside a cell, resulting in dequenching of the probe. Thus, the fluorescence of the pHLIP-FIRE probe is enhanced upon cell-insertion in the targeted tissues but is suppressed elsewhere due to quenching. Targeting studies in mice bearing breast tumors show strong signaling by pHLIP-FIRE, with a contrast index of ∼17, demonstrating (i) direct imaging of pHLIP insertion and (ii) cargo translocation in vivo. Imaging and targeted cargo delivery should each have clinical applications.
authors.affiliation: Department of Molecular Biophysics and Biochemistry, Yale University , New Haven, Connecticut 06511, United States.
authors.forename: Alexander G
authors.initials: AG
authors.lastname: Karabadzhak
authors.forename: Ming
authors.initials: M
authors.lastname: An
authors.forename: Lan
authors.initials: L
authors.lastname: Yao
authors.forename: Rachel
authors.initials: R
authors.lastname: Langenbacher
authors.forename: Anna
authors.initials: A
authors.lastname: Moshnikova
authors.forename: Ramona-Cosmina
authors.initials: RC
authors.lastname: Adochite
authors.forename: Oleg A
authors.initials: OA
authors.lastname: Andreev
authors.forename: Yana K
authors.initials: YK
authors.lastname: Reshetnyak
authors.forename: Donald M
authors.initials: DM
authors.lastname: Engelman
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D005260:Female; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D008969:Molecular Sequence Data; D009369:Neoplasms / Q000175:diagnosis*; D010455:Peptides / Q000737:chemistry
chemical_list: D005456:Fluorescent Dyes; D010455:Peptides