Peroxynitrite-Scavenging Organosilica Nanomedicines for Light-Controllable NO Release and Precision On-Demand Glaucoma Therapy.

Abstract

Nitric oxide (NO) is a promising approach for treating ocular hypertension and glaucoma. However, its clinical application is limited by its uncontrollable release and the unwanted overproduction of peroxynitrite. Herein, a denitrifying hollow mesoporous organosilica nanoparticle (HMMN) with framework cohybridization is first constructed to encapsulate <i>S</i>-nitroso-<i>N</i>-acetyl-d,l-penicillamine (SNAP) to produce SNAP@HMMN with dual capacities of selective peroxynitrite removal and controllable NO release. Featuring a large corneal permeability, the well-designed SNAP@HMMN can achieve trans-corneal delivery to reach the target trabecular meshwork (TM)/Schlemm's canal (SC) site. Upon light irradiation, the intraocular pressure (IOP) is appropriately lowered in an adjustable and long-lasting manner while the outflow tissues are protected from nitrative damage, which is expected to realize precision on-demand glaucoma therapy with little biosafety concern, promising significant clinical translational potential.