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通过多光子激光扫描显微镜对靶向纳米药物递送至朗格汉斯细胞的体内研究。

In vivo study of targeted nanomedicine delivery into Langerhans cells by multiphoton laser scanning microscopy.

作者信息

Kolonics Attila, Csiszovszki Zsolt, Tőke Enikő R, Lőrincz Orsolya, Haluszka Dóra, Szipőcs Róbert

机构信息

Institute for Solid State Physics and Optics of Wigner RCP, Budapest, Hungary; R&D Ultrafast Lasers Ltd, Budapest, Hungary.

出版信息

Exp Dermatol. 2014 Aug;23(8):596-605. doi: 10.1111/exd.12464.

DOI:10.1111/exd.12464
PMID:24903756
Abstract

Epidermal Langerhans cells (LCs) function as professional antigen-presenting cells of the skin. We investigated the LC-targeting properties of a special mannose-moiety-coated pathogen-like synthetic nanomedicine DermaVir (DV), which is capable to express antigens to induce immune responses and kill HIV-infected cells. Our aim was to use multiphoton laser microscopy (MLM) in vivo in order to visualize the uptake of Alexa-labelled DV (AF546-DV) by LCs. Knock-in mice expressing enhanced green fluorescent protein (eGFP) under the control of the langerin gene (CD207) were used to visualize LCs. After 1 h, AF546-DV penetrated the epidermis and entered the eGFP-LCs. The AF546-DV signal was equally distributed inside the LCs. After 9 h, we observed AF546-DV signal accumulation that occurred mainly at the cell body. We demonstrated in live animals that LCs picked up and accumulated the nanoparticles in the cell body.

摘要

表皮朗格汉斯细胞(LCs)作为皮肤的专职抗原呈递细胞发挥作用。我们研究了一种特殊的甘露糖部分包被的病原体样合成纳米药物DermaVir(DV)的LC靶向特性,该药物能够表达抗原以诱导免疫反应并杀死HIV感染细胞。我们的目的是在体内使用多光子激光显微镜(MLM),以便可视化LCs对Alexa标记的DV(AF546-DV)的摄取。利用在朗格汉斯蛋白基因(CD207)控制下表达增强型绿色荧光蛋白(eGFP)的敲入小鼠来可视化LCs。1小时后,AF546-DV穿透表皮并进入eGFP-LCs。AF546-DV信号在LCs内均匀分布。9小时后,我们观察到AF546-DV信号主要在细胞体处积累。我们在活体动物中证明,LCs在细胞体内摄取并积累了纳米颗粒。

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