# Multifunctional Mesoporous Titanium Dioxide Nanodrug for Corneal Haze Treatment and Its Mechanism

## TL;DR

A new nanomedicine called Tet@TiO2 is developed to treat corneal haze after eye surgery by reducing inflammation and preventing complications.

## Contribution

The novel contribution is the development of Tet@TiO2, a multifunctional nanodrug with controlled drug release and anti-inflammatory properties for corneal haze treatment.

## Key findings

- Tet@TiO2 significantly reduced corneal cell edema and collagen fiber expression after surgery.
- Tet@TiO2 inhibited inflammatory factors like α-smooth muscle actin and connective tissue growth factor more effectively than controls.
- Tet@TiO2 modulates the PI3K–AKT–Bax/Bcl-2 pathway to reduce inflammation and prevent corneal haze.

## Abstract

Preventing and treating corneal haze is essential after corneal surface refractive surgery. However, the high intraocular pressure that results after applying traditional anti-inflammatory corticosteroids has attracted great attention. Therefore, we synthesized a multifunctional nanomedicine (Tet@TiO2) with controlled drug release, inflammation targeting, and good biocompatibility for corneal haze treatment. In this study, we discovered that Tet@TiO2 and tetrandrine (Tet), but not TiO2, displayed a characteristic absorption peak at 282 nm. Three weeks after transepithelial photorefractive keratectomy surgery, the Tet@TiO2 group displayed significant decreases in nuclear volume, corneal cell edema, type I and III collagen fiber expression, normal organelle morphology, and collagen fiber arrangement. Compared with those in the control and TiO2 groups, the α-smooth muscle actin, connective tissue growth factor, and type III collagen fibers in the Tet@TiO2 group decreased more significantly after fluorometholone eye drop and Tet treatment, indicating that Tet@TiO2 can effectively inhibit the expression of these inflammatory factors during corneal haze formation. Moreover, Tet@TiO2 showed good, sustained antibacterial properties. More importantly, we found that Tet@TiO2 could effectively down-regulate the expression of phosphatidylinositol 3-kinase (PI3K), protein kinase B (AKT), and B-cell lymphoma-2 (Bcl-2) and up-regulate the expression of Bcl-2-associated X protein (Bax) by modulating the inflammatory PI3K–AKT–Bax/Bcl-2 signaling pathway after corneal surface refractive surgery to effectively prevent and treat corneal haze by reducing the expression of inflammatory factors.