Clickable corneal neovascularization therapy with ROS-responsive polydopamine silica nanoparticles loaded with fenofibrate

Abstract

Corneal neovascularization is a severe eye disease that is often associated with an inflammatory cycle and increased oxidative stress. Excessive reactive oxygen species can cause harmful changes in the corneal epithelium and lead to vicious inflammatory cycles, resulting in an increase in corneal neovascularization. Unfortunately, many drugs used in clinic are water-insoluble and have low bioavailability on the ocular surface, which limits their effectiveness. Therefore, it's crucial to design a new drug delivery system. In this study, we designed an oxide-responsive nanoparticle system called MPA, which was consisted of the large pore sized-mesoporous silica nanoparticles (MSNs) core and the polydopamine (PDA) surface shell via the linkage with disulfide bond. Finally, the nanoparticles are endowed with the enhanced loading efficiency and the controllable release of fenofibrate (Feno) in response to the abundant ROS level in the inflammatory environment. In an in vivo study using mice, treatment with MPA@ Feno resulted in minimal corneal neovascularization area and length and significantly reduced expression of pro-angiogenic factors and oxidative stress factors. Therefore, MPA solves the problem of poor drug solubility, clearing oxygen species in the pathological environment, which will improve its therapeutic effect in corneal neovascularization.