Multifunctional mesoporous titanium dioxide nanodrug for corneal haze treatment and its mechanism

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.