Peroxynitrite-Scavenging Organosilica Nanomedicines for Light-Controllable NO Release and Precision On-Demand Glaucoma Therapy
Maomao Song, Liping Li, Jiamin Liu, Yanting Gao, Mengwei Li, Liming Zhou, Bo Qin, Ajun Xiang, Xinghuai Sun, Wenpei Fan, Yuan Lei, Xiaoyuan Chen
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 S -nitroso- N -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.