In Vivo Laser-Mediated Retinal Ganglion Cell Optoporation Using K V 1.1 Conjugated Gold Nanoparticles

• Published in: Nano letters 2018-11, Vol.18 (11), p.6981-6988
• Main Authors: Wilson, Ariel M, Mazzaferri, Javier, Bergeron, Éric, Patskovsky, Sergiy, Marcoux-Valiquette, Paule, Costantino, Santiago, Sapieha, Przemyslaw, Meunier, Michel
• Format: Article
• Language: English
• ISSN: 1530-6984; 1530-6992
• DOI: 10.1021/acs.nanolett.8b02896

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 K 1.1 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.