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In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using KV1.1 Conjugated Gold Nanoparticles
Nano Letters ( IF 10.8 ) Pub Date : 2018-10-04 00:00:00 , DOI: 10.1021/acs.nanolett.8b02896
Ariel M. Wilson 1 , Javier Mazzaferri , Éric Bergeron 1 , Sergiy Patskovsky 1 , Paule Marcoux-Valiquette 1 , Santiago Costantino , Przemyslaw Sapieha , Michel Meunier 1
Affiliation  

Vision loss caused by retinal diseases affects hundreds of millions of individuals worldwide. The retina is a delicate central nervous system tissue stratified into layers of cells with distinct roles. Currently, there is a void in treatments that selectively target diseased retinal cells, and current therapeutic paradigms present complications associated with off-target effects. Herein, as a proof of concept, we introduce an in vivo method using a femtosecond laser to locally optoporate retinal ganglion cells (RGCs) targeted with functionalized gold nanoparticles (AuNPs). We provide evidence that AuNPs functionalized with an antibody toward the cell-surface voltage-gated K+ channel subunit KV1.1 can selectively deliver fluorescently tagged siRNAs or fluorescein isothiocyanate-dextran dye into retinal cells when irradiated with an 800 nm 100 fs laser. Importantly, neither AuNP administration nor irradiation resulted in RGC death. This system provides a novel, non-viral-based approach that has the potential to selectively target retinal cells in diseased regions while sparing healthy areas and may be harnessed in future cell-specific therapies for retinal degenerative diseases.

中文翻译:

使用K V 1.1共轭金纳米粒子的体内激光介导的视网膜神经节细胞细胞定位。

视网膜疾病引起的视力丧失影响全球数亿个人。视网膜是脆弱的中枢神经系统组织,分层为具有不同作用的细胞层。当前,选择性靶向患病的视网膜细胞的治疗中存在空白,并且当前的治疗范例呈现出与脱靶效应相关的并发症。在本文中,作为概念验证,我们介绍了一种使用飞秒激光的体内方法,以功能化的金纳米颗粒(AuNPs)为目标局部化视网膜神经节细胞(RGCs)。我们提供的证据表明,AuNPs通过针对细胞表面电压门控的K +通道亚基K V的抗体功能化1.1用800 nm 100 fs激光照射时,可以选择性地将荧光标记的siRNA或异硫氰酸荧光素-右旋糖苷染料递送到视网膜细胞中。重要的是,AuNP的施用和辐射均未导致RGC死亡。该系统提供了一种新颖的,非基于病毒的方法,该方法有可能选择性地靶向患病区域的视网膜细胞,同时保留健康区域,并且可以在未来针对视网膜变性疾病的细胞特异性疗法中加以利用。
更新日期:2018-10-04
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