title: Self-assembled quantum dot-peptide bioconjugates for selective intracellular delivery.
abstract: We demonstrate the use of self-assembled luminescent semiconductor quantum dot (QD)-peptide bioconjugates for the selective intracellular labeling of several eukaryotic cell lines. A bifunctional oligoarginine cell penetrating peptide (based on the HIV-1 Tat protein motif) bearing a terminal polyhistidine tract was synthesized and used to facilitate the transmembrane delivery of the QD bioconjugates. The polyhistidine sequence allows the peptide to self-assemble onto the QD surface via metal-affinity interactions while the oligoarginine sequence allows specific QD delivery across the cellular membrane and intracellular labeling as compared to nonconjugated QDs. This peptide-driven delivery is concentration-dependent and thus can be titrated. Upon internalization, QDs display a punctate-like staining pattern in which some, but not all, of the QD signal is colocalized within endosomes. The effects of constant versus limited exposure to QD-peptide conjugates on cellular viability are evaluated by a metabolic specific assay, and clear differences in cytotoxicity are observed. The efficacy of using peptides for selective intracellular delivery is highlighted by performing a multicolor QD labeling, where we found that the presence or absence of peptide on the QD surface controls cellular uptake.
authors.affiliation: Center for Bio/Molecular Science and Engineering, Code 6900, U.S. Naval Research Laboratory, Washington, D.C. 20375, USA. jdelehanty@cbmse.nrl.navy.mil
authors.forename: James B
authors.initials: JB
authors.lastname: Delehanty
authors.forename: Igor L
authors.initials: IL
authors.lastname: Medintz
authors.forename: Thomas
authors.initials: T
authors.lastname: Pons
authors.forename: Florence M
authors.initials: FM
authors.lastname: Brunel
authors.forename: Philip E
authors.initials: PE
authors.lastname: Dawson
authors.forename: Hedi
authors.initials: H
authors.lastname: Mattoussi
mesh_terms: D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D006801:Humans; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology; D011789:Quantum Theory
chemical_list: D010455:Peptides