Committee on Neurobiology, University of Chicago, Chicago, IL 60637, USA.
ASN Neuro. 2012 Oct 23;4(6):383-92. doi: 10.1042/AN20120042.
We have previously shown that CdSe/ZnS core/shell luminescent semiconductor nanocrystals or QDs (quantum dots) coated with PEG [poly(ethylene glycol)]-appended DHLA (dihydrolipoic acid) can bind AcWG(Pal)VKIKKP(9)GGH(6) (Palm1) through the histidine residues. The coating on the QD provides colloidal stability and this peptide complex uniquely allows the QDs to be taken up by cultured cells and readily exit the endosome into the soma. We now show that use of a polyampholyte coating [in which the neutral PEG is replaced by the negatively heterocharged CL4 (compact ligand)], results in the specific targeting of the palmitoylated peptide to neurons in mature rat hippocampal slice cultures. There was no noticeable uptake by astrocytes, oligodendrocytes or microglia (identified by immunocytochemistry), demonstrating neuronal specificity to the overall negatively charged CL4 coating. In addition, EM (electron microscopy) images confirm the endosomal egress ability of the Palm1 peptide by showing a much more disperse cytosolic distribution of the CL4 QDs conjugated to Palm1 compared with CL4 QDs alone. This suggests a novel and robust way of delivering neurotherapeutics to neurons.
我们之前已经表明，经过聚乙二醇（PEG）修饰的二氢硫辛酸（DHLA）修饰的 CdSe/ZnS 核/壳发光半导体纳米晶体或量子点（QD）可以通过组氨酸残基结合 AcWG（棕榈酰基）VKIKKP（9）GGH（6）（Palm1）肽。QD 表面的涂层提供了胶体稳定性，并且这种肽复合物可以使 QD 被培养细胞摄取，并容易从内体进入胞体。我们现在表明，使用聚两性电解质涂层（其中中性的 PEG 被带负电荷的 CL4（紧凑配体）取代）可导致棕榈酰化肽特异性靶向成熟大鼠海马切片培养物中的神经元。星形胶质细胞、少突胶质细胞或小胶质细胞（通过免疫细胞化学鉴定）没有明显摄取，证明了整个带负电荷的 CL4 涂层对神经元的特异性。此外，电子显微镜（EM）图像通过显示与单独的 CL4 QD 相比，与 Palm1 缀合的 CL4 QD 具有更分散的胞质分布，证实了 Palm1 肽的内体出口能力。这表明了一种向神经元递送电神经药物的新的和强大的方法。
