Delivery and tracking of quantum dot peptide bioconjugates in an intact developing avian brain.
Delivery and tracking of quantum dot peptide bioconjugates in an intact developing avian brain.
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DOI：
10.1021/acschemneuro.5b00022
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发表时间：
2015-03-18
影响因子：
5
通讯作者：
Dawson, Glyn
中科院分区：
文献类型：
--
作者：
Agarwal, Rishabh;Domowicz, Miriam S.;Schwartz, Nancy B.;Henry, Judy;Medintz, Igor;Delehanty, James B.;Stewart, Michael H.;Susumu, Kimihiro;Huston, Alan L.;Deschamps, Jeffrey R.;Dawson, Philip E.;Palomo, Valle;Dawson, Glyn
关键词：
发光半导体 ~9.5 nm 纳米粒子（量子点：QD）具有固有的物理化学和光学特性，使我们能够开始了解纳米粒子介导的化学/药物输送的机制。在这里，我们证明了用两性离子紧凑配体功能化的 CdSe/ZnS 核/壳 QD 表面能够将细胞穿透脂肽传递到发育中的鸡胚大脑，而没有任何明显的毒性。功能化的量子点与棕榈酰化肽 WGDap-(棕榈酰)VKIKKP9GGH6 缀合，此前已证明该肽能够独特地促进内体逃逸，并在胚胎第 4 天 (E4) 时显微注射到胚胎鸡脊髓管中。随后，我们能够追踪脊髓延伸至脑室、迁移的神经母细胞、成熟的脑细胞以及脉络丛等复杂结构的标记。 QD 强度延伸到整个大脑，并在 E8 和 E11 之间达到峰值，当时荧光集中在脉络丛中，然后下降到孵化 (E21/P0)。我们观察到胚胎模式或胚胎存活没有异常，mRNA原位杂交证实，在关键发育阶段，与不同脑细胞类型相关的基因（脑脂质结合蛋白、Sox-2、蛋白脂质蛋白和III类-β-微管蛋白）的表达模式均显示出正常的标记模式和强度。我们的研究结果表明，我们可以使用化学修饰的量子点来识别和跟踪神经干细胞的迁移，脉络丛在 E15 后从大脑中清除这些注射的量子点/纳米颗粒，并且它们可以将药物和肽输送到发育中的大脑。
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.
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