Delivery and Tracking of Quantum Dot Peptide Bioconjugates in an Intact Developing Avian Brain

被引:60
作者
Agarwal, Rishabh [1 ]
Domowicz, Miriam S. [2 ]
Schwartz, Nancy B. [2 ]
Henry, Judy [2 ]
Medintz, Igor [3 ]
Delehanty, James B. [3 ]
Stewart, Michael H. [4 ]
Susumu, Kimihiro [4 ]
Huston, Alan L. [4 ]
Deschamps, Jeffrey R. [3 ]
Dawson, Philip E. [5 ]
Palomo, Valle [5 ]
Dawson, Glyn [1 ,6 ,7 ]
机构
[1] Univ Chicago, Comm Neurobiol, Chicago, IL 60637 USA
[2] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
[3] US Naval Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA
[4] US Naval Res Lab, Div Opt Sci, Washington, DC 20375 USA
[5] Scripps Res Inst, La Jolla, CA 92037 USA
[6] Univ Chicago, Dept Pediat, Chicago, IL 60637 USA
[7] Univ Chicago, Dept Biochem & Mol Biol, Chicago, IL 60637 USA
关键词
Nanoparticles; zwitterion; quantum dots; peptidyl delivery; normal embryonic chick brain development; choroid plexus; BIOCOMPATIBLE SEMICONDUCTOR; ZWITTERIONIC LIGANDS; OPTIC TECTUM; MOUSE-BRAIN; SPINAL-CORD; PROTEIN; CELLS; BINDING; NANOPARTICLES; NEUROGENESIS;
D O I
10.1021/acschemneuro.5b00022
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Luminescent semiconductor similar to 9.5 nm nanopartides (quantum dots: QDs) have intrinsic physiochemical and optical properties which enable us to begin to understand the mechanisms of nanopartide 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 E1 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-beta-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 dears these injected QDs/nanoparticles from the brain after E15, and that they can deliver drugs and peptides to the developing brain.
引用
收藏
页码:494 / 504
页数:11
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