title: Delivery and tracking of quantum dot peptide bioconjugates in an intact developing avian brain.
abstract: Luminescent semiconductor ∼9.5 nm nanoparticles (quantum dots: QDs) have intrinsic physiochemical and optical properties which enable us to begin to understand the mechanisms of nanoparticle mediated chemical/drug delivery. Here, we demonstrate the ability of CdSe/ZnS core/shell QDs surface functionalized with a zwitterionic compact ligand to deliver a cell-penetrating lipopeptide to the developing chick embryo brain without any apparent toxicity. Functionalized QDs were conjugated to the palmitoylated peptide WGDap(Palmitoyl)VKIKKP9GGH6, previously shown to uniquely facilitate endosomal escape, and microinjected into the embryonic chick spinal cord canal at embryo day 4 (E4). We were subsequently able to follow the labeling of spinal cord extension into the ventricles, migratory neuroblasts, maturing brain cells, and complex structures such as the choroid plexus. QD intensity extended throughout the brain, and peaked between E8 and E11 when fluorescence was concentrated in the choroid plexus before declining to hatching (E21/P0). We observed no abnormalities in embryonic patterning or embryo survival, and mRNA in situ hybridization confirmed that, at key developmental stages, the expression pattern of genes associated with different brain cell types (brain lipid binding protein, Sox-2, proteolipid protein and Class III-β-Tubulin) all showed a normal labeling pattern and intensity. Our findings suggest that we can use chemically modified QDs to identify and track neural stem cells as they migrate, that the choroid plexus clears these injected QDs/nanoparticles from the brain after E15, and that they can deliver drugs and peptides to the developing brain.
authors: Rishabh
authors: R
authors: Agarwal
authors: Miriam S
authors: MS
authors: Domowicz
authors: Nancy B
authors: NB
authors: Schwartz
authors: Judy
authors: J
authors: Henry
authors: Igor
authors: I
authors: Medintz
authors: James B
authors: JB
authors: Delehanty
authors: Michael H
authors: MH
authors: Stewart
authors: Kimihiro
authors: K
authors: Susumu
authors: Alan L
authors: AL
authors: Huston
authors: Jeffrey R
authors: JR
authors: Deschamps
authors: ⊥Scripps Research Institute, La Jolla, California 92037, United States.
authors: Philip E
authors: PE
authors: Dawson
authors: ⊥Scripps Research Institute, La Jolla, California 92037, United States.
authors: Valle
authors: V
authors: Palomo
authors: #Departments of Pediatrics, Biochemistry and Molecular Biology, University of Chicago, Chicago, Illinois 60637, United States.
authors: Glyn
authors: G
authors: Dawson
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D002642:Chick Embryo; D016503:Drug Delivery Systems; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects / Q000502:physiology; D008845:Microinjections; D008856:Microscopy, Fluorescence; D010455:Peptides / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D045663:Quantum Dots / Q000737:chemistry / Q000378:metabolism*; D012333:RNA, Messenger; D013116:Spinal Cord / Q000187:drug effects / Q000196:embryology / Q000378:metabolism
chemical_list: D010455:Peptides; D012333:RNA, Messenger; D015126:8,11,14-Eicosatrienoic Acid
keywords: Nanoparticles; choroid plexus; normal embryonic chick brain development; peptidyl delivery; quantum dots; zwitterion